6 CLL progressions and 2 RS. After 12 and 24 months of treatment,
the cumulative incidence of discontinuation for the whole cohort was
18% and 32%. In particular, it was 17% and 26% due to AE, 1% and
5% due to CLL relapse, 1% and 3% for RS (Figure 1B). Patients who
discontinued ibrutinib due to AE had a shorter PFS and OS (both p <
0.0001). After a median of 14 months after ibrutinib discontinuation,
the estimated median PFS and TTNT were 11 and 20 months
(Figure 1C). Overall, 22 infective events (9 grade ≥3), 8 atrial fibril-
lations, 8 minors but no major occurred.
Conclusion: We reported the largest real‐life study of ibrutinib in TN
CLL patients with TP53 abn. Discontinuation for AE was associated
with a shorter survival, suggesting that the optimal management of
AE will further contribute to improve the survival of CLL patients.
EA – previously submitted to EHA 2021.
Keywords: Chronic Lymphocytic Leukemia (CLL), Molecular Targeted
Therapies
Conflicts of interests pertinent to the abstract
A. Visentin
Consultant or advisory role: Janssen, Gilead, Abbvie, Italfarmaco
Educational grants: Janssen, Roche, Celgene
135 | IBRUTINIB FOLLOWED BY OFATUMUMAB
CONSOLIDATION IN PREVIOUSLY UNTREATED PATIENTS WITH
CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): GELLC‐7 TRIAL
FROM THE SPANISH GROUP OF CLL (GELLC)
P. Abrisqueta
1
, E. González‐Barca
2
, C. Ferrà
3
, E. Ríos
4
, M. Fernández
de la Mata
5
, J. Delgado
6
, R. Andreu
7
, J. Án. Hernández‐Rivas
8
, M.
José Terol
9
, M. González
10
, M. Belén Vidriales
11
, P. Baltasar
12
, J. De
la Serna
13
, Án. Ramírez Páyer
14
, C. Ballester
15
, C. Moreno
16
, J. A.
García‐Marco
17
, R. Córdoba
18
, L. Yáñez
19
, L. F. Casado
20
, F. Bosch
21
1
Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall
d'Hebron, Hematology, Barcelona, Spain,
2
Instititut Catala D'Oncologia,
Hospital Duran i Reynals, IDIBELL, Universitat de Barcelona, Hematology,
Barcelona, Spain,
3
Instititut Catala D'Oncologia, Hospital Germans Trias i
Pujol, Hematology, Barcelona, Spain,
4
Hospital Nuestra Señora de Valme,
Hematology, Sevilla, Spain,
5
Hospital Universitario Reina Sofía,
Hematology, Córdoba, Spain,
6
Hospital Clínic, Hematology, Barcelona,
Spain,
7
Hospital Universitario La Fe, Hematology, Valencia, Spain,
8
Hospital Infanta Leonor, Hematology, Madrid, Spain,
9
Hospital Clínico
Universitario de Valencia, Hematology, Valencia, Spain,
10
Hospital
Universitario de Salamanca, Hematology, Salamanca, Spain,
11
Hospital
Universitario de Salamanca, Hematology, Salamanca, Spain,
12
Hospital
Universitario La Paz, Hematology, Madrid, Spain,
13
Hospital Universitario
12 de Octubre, Hematology, Madrid, Spain,
14
Hospital Universtiario
Central de Asturias, Hematology, Oviedo, Spain,
15
Hospital Universitari
Son Espases, Hematology, Palma, Spain,
16
Hospital de la Santa Creu i Sant
Pau, Hematology, Barcelona, Spain,
17
Hospital Universitario Puerta de
Hierro, Hematology, Mahadahonda, Spain,
18
Fundación Jiménez Díaz,
Hematology, Madrid, Spain,
19
Hospital Universitario Marqués de
Valdecilla, Hematology, Santander, Spain,
20
Hospital Virgen de la Salud,
Hematology, Toledo, Spain,
21
Vall d'Hebron Institute of Oncology (VHIO),
Hospital Universitari Vall d'Hebron, Hematology, Barcelona, Spain
Introduction: BTK inhibitors have been combined with anti‐CD20
mAbs, but the most appropriate schedule of combining these two
drugs remains to be established. Herein, we present the results of a
multi‐center phase 2 study aimed to determine whether consolida-
tion with ofatumumab improved the response in treatment‐naïve CLL
receiving ibrutinib. (EudraCT 2016‐004937‐26).
Methods: Physically fit (CIRS < 6), treatment‐naïve CLL patients
(pts), received 12 cycles of ibrutinib monotherapy at 420 mg. Patients
attaining CR after this induction were kept on ibrutinib until pro-
gression, whereas those not achieving a CR also continued on ibru-
tinib although received a consolidation with 7 doses of ofatumumab
(300mg D1 and 1,000mg D8 of C13, 1,000 mg D1 of C14‐C18). The
primary endpoint of the study was CR rate assessed after 20 cycles.
Results: 84 pts (median age 69 yrs [38‐84], 71% male) were included.
83% had Binet stage B/C, 61% unmutated IGHV, and 7.6% 17p del/
TP53mut. After completion of 12 cycles of ibrutinib (n = 80), 3 pts
(4%) were in CR, 67 pts (84%) in PR, 6 pts (7%) in PR with lympho-
cytosis (PRL), and 4 pts (5%) in SD. Seventy‐five pts received
FIGURE 1
198
-
SUPPLEMENT ABSTRACTS
consolidation treatment with ofatumumab, whereas the 3 pts in CR
continued on ibrutinib alone and 2 pts discontinued ibrutinib at cycle
12. Six pts discontinued treatment during the consolidation. After
consolidation, 21 pts improved the response from PR to CR, 6 pts
with PRL and 1 pt with SD obtained a PR, 39 pts maintained a PR,
whereas 2 pts persisted in SD. The 3 pts in CR after cycle 12
remained in CR. Seventy‐two pts (86%) completed 20 cycles of
treatment and were evaluable for the primary endpoint, with a CR of
33%. MRD was undetectable in 2 pts (sensitivity 10
‐4
). With a median
FU of 32 months (2 – 40 months), the intention to treat 30‐months
PFS and OS were 89.6% (CI: 82.7–96.5) and 94.6% (CI: 89.5–99.7),
respectively.
At data cut‐off (January 2021), 20 pts had discontinued the
study, 6 of them during the first 12 cycles (PD [n = 1], infections
[n = 2], gastric toxicity [n = 1], patient withdrawal [n = 2]) and 6
during ofatumumab consolidation (PD [n = 1], hematological
toxicity [n = 1], infections [n = 1], second neoplasms [n = 2],
patient withdrawal [n = 1]). Grade ≥3 AEs were experienced by 42
pts (50%), whilst serious AEs were observed in 33 pts (39%). The
most common G3/4 AEs were hematological toxicity (15%) and
infections (13%), while G3/4 infusion‐related reactions were
observed in 3/69 (4%) pts.
Conclusions: This study showed that consolidation with anti‐CD20
therapy after 12 cycles of prior treatment with ibrutinib was well
tolerated and elicited a deeper response. These results support the
potential role of a consolidation therapeutic strategy in CLL, where
the addition of a mAbs in patients with low tumor burden might
improve the quality of the response.
Keywords: Chronic Lymphocytic Leukemia (CLL), Molecular Targeted
Therapies, Combination Therapies
Conflicts of interests pertinent to the abstract
P. Abrisqueta
Consultant or advisory role: Janssen, Abbie, Astrazeneca, Celgene
Honoraria: Janssen, Abbie, Astrazeneca, Celgene, Gilead
136 | FIRST‐LINE TREATMENT WITH IBRUTINIB FOR PATIENTS
WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): 7‐YEAR
RESULTS FROM RESONATE‐2
S. E. Coutre
1
, P. M. Barr
2
, C. Owen
3
, T. Robak
4
, A. Tedeschi
5
, O.
Bairey
6
, J. A. Burger
7
, P. Hillmen
8
, S. Devereux
9
, S. Grosicki
10
, H.
McCarthy
11
, J. Li
12
, D. Simpson
13
, F. Offner
14
, C. Moreno
15
, S. Dai
16
,
A. Szoke
17
, J. P. Dean
18
, T. J. Kipps
19
, P. Ghia
20
1
Stanford Cancer Center, Stanford University School of Medicine, Stanford,
California, USA,
2
Wilmot Cancer Institute, University of Rochester Medical
Center, Clinical Trials Office, Rochester, USA,
3
Tom Baker Cancer Centre,
University of Calgary, Medicine and Oncology, Calgary, Canada,
4
Medical
University of Lodz, Copernicus Memorial Hospital, Hematology, Lodz,
Poland,
5
ASST Grande Ospedale Metropolitano Niguarda, Hematology,
Milan, Italy,
6
Rabin Medical Center, Life and Medicine Sciences, Petah
Tikva, Israel,
7
University of Texas MD Anderson Cancer Center, Leukemia,
Houston, USA,
8
The Leeds Teaching Hospitals, St. James Institute of
Oncology, Oncology, Leeds, UK,
9
Kings College Hospital, NHS Foundation
Trust, Lymphoma Biology, London, UK,
10
School of Public Health, Silesian
Medical University, Hematology and Cancer Prevention, Katowice, Poland,
11
Royal Bournemouth General Hospital, Hematology, Bournemouth, UK,
12
Jiangsu Province Hospital, Hematology, Nanjing, China,
13
North Shore
Hospital, Hematology, Auckland, New Zealand,
14
Universitair Ziekenhuis
Gent, Internal Medicine and Pediatrics, Gent, Belgium,
15
Hospital de la
Santa Creu i Sant Pau, Autonomous University of Barcelona, Hematology,
Barcelona, Spain,
16
Pharmacyclics LLC, an AbbVie Company, Biostatistics,
Sunnyvale, USA,
17
Pharmacyclics LLC, an AbbVie Company, Oncology,
Sunnyvale, USA,
18
Pharmacyclics LLC, an AbbVie Company, Oncology,
Sunnyvale, USA,
19
UCSD Moores Cancer Center, Blood Cancer Research
Fund, San Diego, USA,
20
Università Vita‐Salute San Raffaele and IRCCS
Ospedale San Raffaele, Medical Oncology, Milan, Italy
Introduction: Ibrutinib, a once‐daily Bruton's tyrosine kinase inhibi-
tor, is the only targeted therapy with significant progression‐free
survival (PFS) and overall survival (OS) benefit in multiple random-
ized phase 3 studies versus established therapies in patients (pts)
with previously untreated CLL/small lymphocytic lymphoma (SLL).
Here we report extended long‐term follow‐up data of first‐line
ibrutinib vs chlorambucil in older pts with CLL/SLL from the
RESONATE‐2 study.
Methods: RESONATE‐2 is a phase 3 study that enrolled older pts
(≥65 y) with previously untreated CLL/SLL. Pts with del(17p) were
excluded. Pts (N = 269) were randomly assigned 1:1 to once‐daily
single‐agent ibrutinib 420 mg (n = 136) until disease progression
(PD) or unacceptable toxicity or to chlorambucil 0.5–0.8 mg/kg (n =
133) up to 12 cycles. PFS, OS, overall response rate (ORR), and safety
are reported. Long‐term responses were assessed by investigator per
2008 iwCLL criteria.
Results: With up to 7y of follow‐up (median 74.9 mo; range 0.1–
86.8), significant PFS benefit was sustained for pts treated with
ibrutinib vs chlorambucil (hazard ratio [HR] 0.160 [95% confidence
interval (CI) 0.111–0.230]). The PFS rate at 6.5y was 61% vs 9% in
pts treated with ibrutinib vs chlorambucil. PFS benefit was
observed in ibrutinib‐treated pts across all subgroups, including in
pts with high‐risk genomic features of unmutated IGHV (HR 0.109
[95% CI 0.063–0.189]) or del(11q) (HR 0.033 [95% CI 0.010–
0.107]). With ibrutinib treatment, OS rate was 78% at 6.5y. For
ibrutinib‐treated pts, ORR was 92% with complete response (CR/
CRi) rate increasing to 34% at the current follow‐up. Ongoing
rates of grade ≥3 adverse events (AEs) of interest remained low
for hypertension (5–6y interval: 5%, n = 4; 6–7y: 4%, n = 3) and
atrial fibrillation (5–6y: 1%, n = 1; 6–7y: 1%, n = 1); no grade ≥3
major hemorrhage occurred in 5–7y. Dose reductions due to grade
≥3 AEs occurred in 1% (n = 1 each) of pts during 5–6y and 6–7y
intervals. Across total follow‐up, dose reductions due to any grade
AEs were reported for 31 pts, of whom 22/31 (71%) had resolu-
tion/improvement of the AE. The primary reason for discontinua-
tions in 5–7y was PD (5–6y: 5%, n = 4; 6–7y: 6%, n = 4). Any
SUPPLEMENT ABSTRACTS
-
199
grade AEs leading to discontinuations were seen in 3% (n = 2) of
pts from 5–6y and none in 6–7y. 47% of pts remain on single‐
agent ibrutinib with up to 7y of follow‐up.
Conclusions: The use of first‐line ibrutinib treatment led to sustained
PFS, including for pts with high‐risk genomic features, and OS benefit
for pts with CLL/SLL with extended long‐term follow‐up in
RESONATE‐2. Over time, responses continue to deepen. Rates of
grade ≥3 AEs of interest continued to be low at up to 7y follow‐up.
Further discontinuations and dose reductions due to AEs were rare,
and most AEs leading to dose reduction resolved or improved.
Ibrutinib remains well tolerated with no new safety signals observed.
EA – previously submitted to ASCO and EHA 2021.
The research was funded by: Pharmacyclics LLC, an AbbVie Company
Keywords: Molecular Targeted Therapies, Chronic Lymphocytic
Leukemia (CLL)
Conflicts of interests pertinent to the abstract
S. E. Coutre
Consultant or advisory role: AbbVie, Adaptive, AstraZeneca, Celgene,
Genentech, Novartis, BeiGene, Janssen, Pharmacyclics LLC, an Abb-
Vie Company
Honoraria: AbbVie, Janssen, Pharmacyclics LLC, an AbbVie Company
Research funding: AbbVie, Janssen, Pharmacyclics LLC, an AbbVie
Company, AstraZeneca
Other remuneration: Expert testimony: Genentech, Janssen
P. M. Barr
Consultant or advisory role: Celgene, Pharmacyclics LLC, an AbbVie
Company, AbbVie, Gilead, SeaGen, Merck, Genentech, Janssen,
MorphoSys, AstraZeneca, TG Therapeutics
C. Owen
Honoraria: AbbVie, Janssen, AstraZeneca, Merck, Teva, Roche,
Gilead, Incyte
T. Robak
Consultant or advisory role: Janssen, AstraZeneca, Acerta
Honoraria: AstraZeneca, Janssen
Research funding: Janssen, AstraZeneca, Acerta
A. Tedeschi
Honoraria: Janssen, BeiGene, AstraZeneca, AbbVie
Other remuneration: Speakers bureau: Janssen, BeiGene, AstraZe-
neca, AbbVie
O. Bairey
Consultant or advisory role: AbbVie, AstraZeneca, Janssen
Research funding: Janssen
J. A. Burger
Consultant or advisory role: Janssen
Honoraria: Janssen
Research funding: Gilead, TG Therapeutics, Pharmacyclics LLC, an
AbbVie Company, BeiGene
Educational grants: Gilead, TG Therapeutics, Pharmacyclics LLC, an
AbbVie Company, Novartis, Janssen
Other remuneration: Speakers bureau: Gilead, TG Therapeutics,
Pharmacyclics LLC, an AbbVie Company, Novartis, Janssen
P. Hillmen
Consultant or advisory role: Janssen, AbbVie, BeiGene
Research funding: Janssen, AbbVie, Pharmacyclics LLC, an AbbVie
Company, Celgene
Educational grants: Janssen, AbbVie, Roche
FIGURE:
Investigator‐Assessed Progression‐Free Survival
200
-
SUPPLEMENT ABSTRACTS
H. McCarthy
Consultant or advisory role: Janssen, AbbVie
Honoraria: Janssen
Other remuneration: Travel, accommodations, expenses: Janssen
D. Simpson
Employment or leadership position: BeiGene
Stock ownership: BeiGene
Honoraria: AbbVie, Janssen
Research funding: Sanofi, AbbVie, BeiGene, GSK, Roche, Amgen,
Janssen, Pharmacyclics LLC, an AbbVie Company, Acerta, Merck
Sharp & Dohme, Celgene
Educational grants: AbbVie, Janssen
C. Moreno
Consultant or advisory role: Janssen, AbbVie, AstraZeneca, BeiGene
Research funding: AbbVie, Janssen
Other remuneration: Speakers bureau: Janssen
S. Dai
Employment or leadership position: AbbVie, Horizon Therapeutics
A. Szoke
Employment or leadership position: Pharmacyclics LLC, an AbbVie
Company
Stock ownership: AbbVie
J. P. Dean
Employment or leadership position: Pharmacyclics LLC, an AbbVie
Company
Stock ownership: Pharmacyclics LLC, an AbbVie Company
T. J. Kipps
Employment or leadership position: Moores Cancer Center; Patents,
etc: Cirmtuzumab was developed by this author and licensed by
University of California to Oncternal Therapeutics, which provided
stock options and research funding to the author's laboratory.
Consultant or advisory role: AbbVie, Genentech‐Roche, Gilead, Phar-
macyclics, an AbbVie Company, Celgene, Janssen, DavaOncology
Stock ownership: Oncternal Therapeutics
Honoraria: Pharmacyclics, an AbbVie Company, AbbVie, Janssen,
Celgene, Genentech, Roche, Gilead Sciences, DavaOncology
Research funding: Pharmacyclics LLC, an AbbVie Company, MD
Anderson Cancer Center, Oncternal Therapeutics, Crim, Velos,
Celgene
Educational grants: AbbVie, Pharmacyclics LLC, an AbbVie Company,
Genentech, Roche, Janssen, Gilead, Celgene, Indy Hematology Re-
view, DavaOncology, G‐Therapeutics, Verastem, Bionest Partners,
OncLive
Other remuneration: Speakers bureau: Verastem, Pharmacyclics LLC,
an AbbVie Company, Janssen, AbbVie, Genentech, Gilead, Dava
Pharmaceuticals
P. Ghia
Consultant or advisory role: AbbVie, Acerta/AstraZeneca, Adaptive,
ArQule, BeiGene, Celgene/Juno, Gilead, Janssen, Lilly/Loxo, Sunesis
Honoraria: AbbVie, Acerta/AstraZeneca, Adaptive, ArQule, BeiGene,
Celgene/Juno, Gilead, Janssen, Lilly/Loxo, Sunesis
Research funding: AbbVie, Gilead, Janssen, Novartis, Sunesis
137 | VENETOCLAX‐OBINUTUZUMAB FOR PREVIOUSLY
UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA: 4‐YEAR
FOLLOW‐UP ANALYSIS OF THE RANDOMIZED CLL14 STUDY
O. Al‐Sawaf
1
, C. Zhang
1
, S. Robrecht
1
, M. Tandon
2
, A. Panchal
2
, A.‐M.
Fink
1
, E. Tausch
3
, M. Ritgen
4
, K.‐A. Kreuzer
1
, S. Kim
5
, C. Wendtner
6
,
B. Eichhorst
1
, S. Stilgenbauer
3
, Y. Jiang
7
, M. Hallek
1
, K. Fischer
1
1
University Hospital of Cologne, Department I of Internal Medicine,
Cologne, Germany,
2
Roche Products Limited, Welwyn Garden City, UK,
3
University Hospital Ulm, Department III of Internal Medicine, Ulm,
Germany,
4
University of Schleswig‐Holstein, Department II of Internal
Medicine, Kiel, Germany,
5
AbbVie Inc., Chicago, USA,
6
Klinikum
Schwabing, Department of Hematology, Oncology, Immunology, Palliative
Care, Infectious Diseases and Tropical Medicine, Munich, Germany,
7
Genentec Inc., San Francisco, USA
Introduction: The CLL14 study showed significant improvement of
progression‐free survival (PFS) and rates of undetectable minimal
residual disease (uMRD) with venetoclax‐obinutuzumab (Ven‐Obi) as
compared to chlorambucil‐obinutuzumab (Clb‐Obi) in patients (pts)
with previously untreated chronic lymphocytic leukemia (CLL) and
coexisting conditions. The aim of this report is to provide updated
efficacy and safety data from the ongoing follow‐up of the CLL14
study with now all pts being off study treatment for at least 3 years.
Methods: Pts with previously untreated CLL and coexisting condi-
tions were randomized 1:1 to receive 12 cycles of Ven with 6 cycles
of Obi or 12 cycles of Clb with 6 cycles of Obi. Primary endpoint was
investigator‐assessed PFS. Key secondary endpoints were safety,
response rates, rates of minimal residual disease (MRD) and overall
survival.
Results: Of the 432 enrolled pts, 216 were randomly assigned to
receive Ven‐Obi and 216 to receive Clb‐Obi. After a median follow‐
up of 52.4 months (interquartile range 49.5‐56.2), PFS continued to
be superior for Ven‐Obi as compared to Clb‐Obi (median not reached
(nr) vs. 36.4 months; HR 0.33 [95% CI 0.25‐0.45], p < 0.0001)(Fig A).
At 4 years after randomization, the estimated PFS rate was 74.0% in
the Ven‐Obi arm and 35.4% in the Clb‐Obi arm. This improvement
was observed across all clinical and biological risk groups, including
pts with TP53 mutation/deletion (4‐year PFS 53.0% vs 20.8%) and
unmutated IGHV status (4‐year PFS 68.0% vs 19.8%)(Fig B,C).
Overall, 35 disease progressions in the Ven‐Obi arm have been
observed, compared to 122 in the Clb‐Obi arm. Time to next treat-
ment was significantly longer in the Ven‐Obi arm (4‐year TTNT
81.1% vs 59.9%; HR 0.46, 95% CI [0.32‐0.65], p < 0.0001)(Fig D). The
majority of pts received and responded to BTK inhibitor mono-
therapy as a second‐line treatment after progressive disease in both
arms (57.1% in Ven‐Obi arm, 55.6% in Clb‐Obi arm).
SUPPLEMENT ABSTRACTS
-
201
Assessment of MRD by NGS in peripheral blood 30 months after
the end of treatment showed that 26.9% of pts in the Ven‐Obi arm
had uMRD (<10
‒4
), 21.8% had low (L)‐MRD (≥10
‒4
and <10
‒2
) and
13.4% high (H)‐MRD (≥10
‒2
), compared to 3.2% uMRD, 8.8%%
L‐MRD, 28.2% H‐MRD in the Clb‐Obi arm.
No difference in overall survival has been observed between the
Ven‐Obi and Clb‐Obi arm; at 4 years 85.4% pts were alive in the Ven‐
Obi arm and 83.1% in the Clb‐Obi arm (HR 0.85 [0.54‐1.35], p = 0.49)
(Fig E). Second primary malignancies were reported in 40 (18.9%) pts
in the Ven‐Obi arm and 30 (14.0%) in the Clb‐Obi arm. No new safety
signals were observed.
Conclusion: The 4‐year follow‐up confirms the superior efficacy with
longer PFS and deep remissions after fixed‐duration Ven‐Obi
compared to Clb‐Obi. The majority of pts remains without relapse
three years after completing Ven‐Obi therapy. Fixed‐duration Ven‐
Obi continues to be an effective treatment for all pts with CLL and
coexisting conditions.
EA – previously submitted to EHA 2021.
The research was funded by: Hoffmann‐La Roche Ltd.; AbbVie Inc.
Keywords: Combination Therapies, Chronic Lymphocytic Leukemia
(CLL)
Conflicts of interests pertinent to the abstract
O. Al‐Sawaf
Honoraria: Roche, AbbVie, Janssen, Gilead, AstraZeneca
Research funding: Roche, AbbVie, Janssen, Beigene
Educational grants: Roche, AbbVie, Janssen, Gilead, AstraZeneca
M. Tandon
Employment or leadership position: Roche Products Ltd
Stock ownership: Roche Products Ltd.
A. Panchal
Employment or leadership position: Roche Products Ltd.
A.‐M. Fink
Honoraria: Celgene, Janssen, Hoffmann‐LaRoche
E. Tausch
Honoraria: Roche, AbbVie
FIGURE 1
202
-
SUPPLEMENT ABSTRACTS
M. Ritgen
Honoraria: Hoffmann‐LaRoche, AbbVie
Research funding: Hoffman‐LaRoche
K.‐A. Kreuzer
Honoraria: Hoffmann‐LaRoche, AbbVie
Research funding: Roche, AbbVie
S. Kim
Employment or leadership position: AbbVie
C. Wendtner
Honoraria: Hoffmann‐LaRoche, AbbVie, Janssen‐Cilag, Gilead,
MorphoSys
B. Eichhorst
Honoraria: Hoffmann‐LaRoche, AbbVie, Celgene, Bovartis, ArQule,
BeiGene, Gilead, AstraZeneca, Oxford Biomedica (UK), Adaptive
Biotechnologies
Research funding: Hoffmann‐LaRoche, AbbVie, Janssen
S. Stilgenbauer
Honoraria: AbbVie, AstraZeneca, Celgene, Gilead, GSK, Hoffmann La‐
Roche, Janssen, Novartis, Pharmacyclics, Sunesis, Verastem
Research funding: AbbVie, AstraZeneca, Celgene, Gilead, GSK,
Hoffmann La‐Roche, Janssen, Novartis, Pharmacyclics, Sunesis,
Verastem
Y. Jiang
Employment or leadership position: Genentec Inc.
M. Hallek
Honoraria: Roche, Gilead, Mundipharma, Janssen, Celgene, Pharma-
cyclics, AbbVie, Boehringer Ingelheim
Research funding: Roche, Gilead, Mundipharma, Janssen, Celgene,
Pharmacyclics, AbbVie
K. Fischer
Honoraria: AbbVie, Hoffmann‐LaRoche
138 | UNFAVORABLE GENETICS IMPACT MRD RESPONSE TO
VENETOCLAX+RITUXIMAB RETREATMENT IN RELAPSED OR
REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA (R/R CLL):
PHASE 3 MURANO SUBSTUDY
J. Q. Wu
1
, J. F. Seymour
2
, B. Eichhorst
3
, P. Hillmen
4
, T. Kipps
5
,
A. W. Langerak
6
, C. Owen
7
, J. Dubois
8
, C. Mellink
8
, A. van der Kevie‐
Kersemaekers
8
, B. Chyla
9
, Y. Jiang
1
, M. Boyer
10
, M. Thadani‐
Mulero
10
, M. Lefebure
10
, A. P. Kater
8
1
Genentech, Inc, Oncology Biomarker Development, South San Francisco,
USA,
2
Royal Melbourne Hospital, Peter MacCallum Cancer Centre and
University of Melbourne, Department of Haematology, Melbourne,
Australia,
3
University of Cologne, Department I of Internal Medicine and
Center of Integrated Oncology Aachen, Cologne, Germany,
4
St. James's
University Hospital, Department of Haematology, Leeds, UK,
5
UC San
Diego Health, Moores Cancer Center, San Diego, USA,
6
University Medical
Center, Department of Hematology, Erasmus MC, Rotterdam,
Netherlands,
7
University of Calgary, Departments of Medicine and
Oncology, Calgary, Canada,
8
Cancer Center Amsterdam, Amsterdam
University Medical Centers, University of Amsterdam, Department of
Hematology, Amsterdam, Netherlands,
9
AbbVie Inc., Cancer Biomarkers,
North Chicago, USA,
10
Roche Products Limited, Clinical Science, Welwyn
Garden City, UK
Introduction: At the MURANO trial (NCT02005471) 5‐yr update,
median (95% CI) progression‐free survival (PFS) was 54 (48–57) mo
with venetoclax‐rituximab (VenR) and 17 (15–22) mo with
bendamustine‐R (BR); 36% of pts on VenR and 63% on BR had
received new anti‐CLL therapy. A substudy from 2018 onward
enrolled 34 R/R CLL pts with progressive disease (PD) after initial
treatment (tx) to receive VenR as re‐tx (n = 25) or crossover from BR
(n = 9). We report on pts who had PD (median [range] PFS 46 [36–
58] mo), required anti‐CLL therapy, and were retreated with VenR.
Molecular changes from the main study baseline (BL‐1) to re‐tx
baseline (BL‐2) were assessed, as were BL‐2 genetic features and
their association with minimal residual disease (MRD) response to
VenR.
Methods: Pts received Ven 400mg/d for 2 yrs and monthly R for the
first 6 mo. Genomic complexity (GC; defined by copy number alter-
ations [CNA]: 0–2 non‐complex, 3–4 low, ≥5 high) was assessed by
aCGH, chromosomal abnormalities by aCGH + FISH (high clone
≥20%, low clone 7–19%) and peripheral blood MRD by PCR and/or
flow cytometry (undetectable [u]MRD threshold of <10
‐4
).
Results: At data cutoff (Oct 13 2020), 25 pts were retreated with
VenR; median (range) follow‐up of 12 (3–21) mo and tx‐free interval
of 28 (12–38) mo. Unfavorable genetic characteristics were enriched
from BL‐1 to BL‐2. At BL‐2, 14/24 pts had del(17p) including 11 high
clones: 3 newly acquired and 4 shifted from low to high. Median
(range) CNA increased from 3 (1–6) at BL‐1 to 4 (1–15) at BL‐2 (P <
0.05). 11/20 pts had GC (8 high GC) at BL‐2 with either new chro-
mosomal abnormalities or increased clone size in poor prognostic
lesions (2p and 8q gain; 7q, 8p, 11q and 18p loss).
Investigator‐assessed objective response rate was 70% (14/20
evaluable pts; 50% [14/25] among ITT pts; 5 complete response, 9
partial response). Of 17 pts with MRD data at the re‐tx end of
combination tx (R‐EOCT), 5 achieved uMRD and 12 were MRD+
(Figure). 16 pts had evaluable del(17p) results. Of 6 pts without del
(17p) at BL‐2, 4 attained uMRD at R‐EOCT while all 10 with del(17p)
at BL‐2 were MRD+ at R‐EOCT. Of these, 4/10 had new del(17p)
from BL‐1 or had evolved from low to high clone. GC status was
available for 14 pts. Of 4 pts without GC at BL‐2, 2 attained uMRD at
R‐EOCT. Of 10 pts with GC at BL‐2, 8 were MRD+ and 2 had uMRD
at R‐EOCT; 5/10 had new or increased GC from BL‐1. Of 10 pts with
uMRD at main study EOCT, 4 re‐attained uMRD at R‐EOCT. Among
the 6 unable to re‐attain uMRD, 83% (5/6) had del(17p) at BL‐2 (3
newly evolved from BL‐1) vs 40% (2/5) at BL‐1.
Conclusions: Pts with PD after initial VenR tx had unfavorable bio-
logical characteristics at BL‐2. There was a genetic profile shift from
BL‐1 to BL‐2, with greater GC and increased del(17p) prevalence and
SUPPLEMENT ABSTRACTS
-
203
clonality. Higher prevalence of genetic risk factors negatively
impacted MRD response to re‐tx at the R‐EOCT. Deep initial
response with favorable BL‐2 characteristics predict uMRD attain-
ment with VenR re‐tx.
EA – previously submitted to EHA 2021.
The research was funded by: Venetoclax is being developed in
collaboration between Genentech Inc. and AbbVie. Genentech Inc.
and AbbVie provided financial support for the MURANO trial and
participated in the design, study conduct, analysis and interpretation
of data, as well as the writing, review, and approval of the abstract.
Third‐party editorial assistance, under the direction of Jenny Wu,
was provided by Sinéad Holland of Ashfield MedComms, an Ashfield
Health company, and was funded by F. Hoffmann‐La Roche Ltd.
Keywords: Diagnostic and Prognostic Biomarkers, Minimal residual
disease, Chronic Lymphocytic Leukemia (CLL)
Conflicts of interests pertinent to the abstract
J. Q. Wu
Employment or leadership position: Genentech Inc. / F. Hoffmann‐La
Roche Ltd
Stock ownership: Genentech Inc. / F. Hoffmann‐La Roche Ltd
J. F. Seymour
Consultant or advisory role: Roche
Honoraria: AbbVie, Astra Zeneca, Gilead, Jannsen, Mei Pharma,
Nurix, Roche
Research funding: AbbVie, Celgene, Jannsen, Roche
Other remuneration: Speaker's bureau: AbbVie, Roche; Membership
on an entity's Board of Directors or advisory committees: AbbVie,
AstraZeneca, Roche
B. Eichhorst
Employment or leadership position: University Hospital of Cologne
Consultant or advisory role: Janssen, Roche, Novartis, AbbVie, Gilead,
Celgene, ArQule, AstraZeneca, Oxford Biomedica (UK), BeiGene
P. Hillmen
Employment or leadership position: Professor of Experimental Hae-
matology, University of Leeds, Worsley Building, Leeds
Consultant or advisory role: Janssen, Pharmacyclics, Abbvie, Roche,
Gilead, Apellis
Honoraria: Janssen, Abbvie, AstraZeneca, Verastem, Apellis and
Alexion, Pharmacyclics, BeiGene, Juno, Roche
Research funding: Janssen, Pharmacyclics, Abbvie, Roche, Gilead,
Apellis
FIGURE: Increased del(17p) clonality and GC negativity impact MRD response at R‐EOCT
204
-
SUPPLEMENT ABSTRACTS
Other remuneration: Speaker's bureau: Abbvie, Janssen, Pharmacy-
clics, Gilead, Roche, AstraZeneca, Alexion, Juno/BMS, Apellis,
BeiGene
T. Kipps
Employment or leadership position: University of California, San
Diego
Honoraria: Travel/ Honoraria 2019‐2021: Pharmacyclics/Abbvie,
Genentech, Janssen, Dava Oncology, iwNHL, TG Therapeutics, Cel-
gene, Velosbio•Astra Zeneca, Loxo Oncology
Research funding: National Cancer Institute/NIH, Breast Cancer
Research Foundation, Oncternal Therapeutics, Inc., California Insti-
tute for Regenerative Medicine, Specialized Center of Research,
Leukemia and Lymphoma Society
Other remuneration: Cirmtuzumab was developed by T.J.K. in the T.J.
K. laboratory and licensed by the University of California to Onc-
ternal Therapeutics, Inc., which provided stock options and research
funding to the T.J.K. laboratory. T.J.K. has received research funding
and/or has served as an advisor to Oncternal, Pharmacyclics/Abbvie,
Genentech, Janssen, Astra Zeneca, Pharmacyclics, and Velos Bio.
Cirmtuzumab was developed by T.J.K.and licensed by the University
of California to Oncternal Therapeutics, Inc., which has provided
stock/options to the university and T.J.K
A. W. Langerak
Research funding: Roche‐Genentech, Gilead
Other remuneration: Speaker's bureau: Janssen
C. Owen
Consultant or advisory role: AbbVie, AstraZeneca, Janssen, Merck,
Roche, Incyte, Novartis, Gilead
Honoraria: AbbVie, Roche, Janssen, Astrazeneca, Merck, Servier,
Novartis, Teva
J. Dubois
Research funding: Genentech, Roche
C. Mellink
Employment or leadership position: Amsterdam University Medical
Centre
Research funding: Genentech funding for microarray analysis
A. van der Kevie‐Kersemaekers
Employment or leadership position: Amsterdam University Medical
Centre
Research funding: Genentech funding for microarray analysis
B. Chyla
Employment or leadership position: Abbvie
Stock ownership: Abbvie
Y. Jiang
Employment or leadership position: Genentech
Stock ownership: Roche
M. Boyer
Employment or leadership position: Roche
Stock ownership: Roche
M. Thadani‐Mulero
Employment or leadership position: Roche Products Limited
Stock ownership: Roche Products Limited
M. Lefebure
Employment or leadership position: Roche
Stock ownership: Roche
A. P. Kater
Employment or leadership position: Amsterdam University Medical
Centers
Consultant or advisory role: Biogeneration, LAVA
Honoraria: Celgene, Roche/Genentech, AstraZeneca, Janssen
Research funding: Celgene, Roche/Genentech, AstraZeneca, Janssen
139 | A CONTINUOUS INDIVIDUALIZED RISK INDEX FOR
REFINED OUTCOME PREDICTION AFTER TARGETED THERAPY
FOR PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CIRI‐
CLL)
O. Al‐Sawaf
1
, M. S. Esfahani
2
, C. Zhang
1
, E. Tausch
3
, A. Schilhabel
4
, B.
Eichhorst
1
, S. Stilgenbauer
3
, M. Hallek
1
, A. A. Alizadeh
2
, D. M. Kurtz
2
,
K. Fischer
1
1
University Hospital of Cologne, Department I of Internal Medicine,
Cologne, Germany,
2
Stanford University, Divisions of Oncology &
Hematology, Department of Medicine, Stanford, USA,
3
University Hospital
Ulm, Department III of Internal Medicine, Ulm, Germany,
4
University of
Schleswig‐Holstein, Department II of Internal Medicine, Kiel, Germany
Introduction: The continuous individualized risk index (CIRI) is a
recently described Bayesian framework to dynamically determine
outcome probabilities for individual patients (pts) by integrating
diverse factors over time, including minimal residual disease (MRD)
measurements in the context of chemoimmunotherapy (Kurtz et al
2019). Here, we explore if CIRI can be applied in the context of novel
targeted treatments for pts with CLL.
Methods: We developed a refined CIRI‐CLL that also included
venetoclax‐treated pts. We used a previously defined development
set from the CLL8/10/11 randomized trials (FC [±R], BR, Clb [±R/
Obi], n = 699) to establish key “prior” parameters for previously
established factors, including CLL‐IPI (age, IGHV, TP53del/mut,
Binet/Rai and ß2M), therapy effect, and MRD levels. Therapeutic
effect of venetoclax (Ven) was established from the published
MURANO Ph3 trial data (Ven‐R). We then applied this updated CIRI
model in an independent validation set of 432 pts from CLL14 (Ven‐
Obi vs Clb‐Obi) to predict PFS and compared performance to other
indices. To capture the nonuniform change in PFS following therapy
coinciding with end of fixed‐duration therapy, we utilized piecewise
proportional hazard modeling with a single change‐point at 18
months in a modified Bayesian model. We then re‐assessed calibra-
tion and performance for CIRI‐CLL in pts treated with Ven‐Obi.
Results: We first applied CLL‐IPI (previously established for che-
moimmunotherapy) to pts treated with Ven‐Obi, and observed
SUPPLEMENT ABSTRACTS
-
205
significantly shorter PFS (P = 0.007) in comparing pts with very high
vs low risk (Fig C). Outcomes after Ven‐Obi did not differ signifi-
cantly for high vs intermediate risk CLL‐IPI groups (Fig C). We tested
if CIRI might improve upon CLL‐IPI by comparing CIRI and CLL‐IPI
for prognostic value in the full CLL14 validation set. CIRI demon-
strated good calibration with <7% difference between observed and
predicted event probabilities (Fig A). The performance was signifi-
cantly improved compared to CLL‐IPI seen by 23‐30% improvements
in the C‐statistic from 1‐5 yrs. (p < 0.001; Fig B), including superior
prediction to single‐factor indices, such as treatment choice or MRD
status (Fig B). Performance was maintained when limiting to Ven‐Obi
treated pts only (Fig E). Notably, CIRI allowed for expected risk
stratification for 3‐yr PFS with appropriately stratified high, inter-
mediate and low‐risk groups (Fig D). In the full CLL14 validation set,
pts with low‐CIRI risk had the longest PFS (3‐yr PFS from most
recent landmark 77.1%) compared to ≤9.4% for high‐CIRI risk
subset.
Conclusions: These results validate CIRI in the context of targeted
treatment of CLL. Therefore, CIRI provides a dynamic risk model with
robust risk stratification that can be extended to newer fixed‐
206
-
SUPPLEMENT ABSTRACTS
duration therapies, with important implications for future risk‐
adapted CLL trials.
Keywords: Chronic Lymphocytic Leukemia (CLL)
Conflicts of interests pertinent to the abstract
O. Al‐Sawaf
Consultant or advisory role: Roche, Abbvie
Honoraria: Roche, Abbvie
Research funding: Roche, Abbvie
Educational grants: Roche, Abbvie
E. Tausch
Honoraria: Roche AG, AbbVie
B. Eichhorst
Honoraria: Hoffmann‐La Roche, AbbVie, Celgene, Novartis, ArQule,
BeiGene, Gilead, AstraZeneca, Oxford Biomedica (UK), Adaptive
Biotechnologies
Research funding: Hoffmann‐LaRoche, AbbVie, Janssen
S. Stilgenbauer
Honoraria: AbbVie, AstraZeneca, Celgene, Gilead, GSK, Hoffmann La‐
Roche, Janssen, Novartis, Pharmacyclics, Sunesis, Verastem
Research funding: AbbVie, AstraZeneca, Celgene, Gilead, GSK, Hoff-
mann La‐Roche, Janssen, Novartis, Pharmacyclics, Sunesis, Verastem
M. Hallek
Honoraria: Roche, Gilead, Mundipharma, Janssen, Celgene, Pharma-
cyclics, AbbVie
Research funding: Roche, Gilead, Mundipharma, Janssen, Celgene,
Pharmacyclics, AbbVie
K. Fischer
Honoraria: AbbVie, Hoffmann‐LaRoche
140 | A CROSS‐SECTIONAL STUDY ON THE GLOBAL
DIFFERENCES IN INFORMATION EXPERIENCES AND NEEDS OF
PATIENTS WITH LYMPHOMA AND CLL
L. Warwick
1
, O. Bamigbola
2
, N. Dren
2
1
Lymphoma Coalition, Administrative, Mississauga, Canada
2
, Lymphoma
Coalition, Research, Mississauga, Canada
Background: Patient‐centricity remains a cornerstone in the care
of patients with lymphoma and CLL, as informed patients are
TABLE 1 Patients' information experience at diagnose' and areas of need for more information' by region
SUPPLEMENT ABSTRACTS
-
207
consistently associated with better outcomes and healthcare
experiences.
Aims: This study uses the Lymphoma Coalition (LC) 2020 Global
Patient Survey (GPS) on Lymphomas and CLL to describe the global
differences in patients’ information experiences at diagnosis, as well
as to compare the areas of need for more information.
Methods: Globally, 9,179 patients with lymphoma or CLL from 89
countries took part in the LC 2020 GPS. The countries were grouped
into regions, and regions with greater than 200 patient respondents
were included in the analysis. The five regions analysed were Asia
(AS) (n = 2326), Oceania (OC) (n = 695), Europe (EU)(n = 4343),
North America (NA) (n = 1543), and South America (SA) (n = 214).
Descriptive analyses of questions relating to patients’ informa-
tion experiences at diagnoses and areas in which they needed more
information were performed in IBM SPSS v27.
Results: All the regions differed significantly (p < 0.05) in the de-
mographic categories of age, sex, education level, and household
status.
When asked which time point patients had the greatest need for
information, over half of patients in all the regions reported the time
point as ‘within the first month following diagnosis’ (AS‐62%, OC‐
58%, EU‐57%, NA‐53% and SA‐59%) (Table 1).
Relating to how patients felt about the amount of information
they were given upon diagnosis with lymphoma, patients from AS
were the most prevalent in reporting they were not given enough
information (55%) followed by patients from NA (36%). Additionally,
only 30% of patients from AS reported receiving the right amount
of information, while 60% and more, of patients from NA, EU, SA,
and OC reported the same (60%, 67%, 71% and 70% respectively)
(Table 1).
When asked about the specific areas patients needed more in-
formation in, the most commonly reported areas in all the regions were
‘treatment options’ (AS‐76%, OC‐44%, EU‐50%, NA‐61% and SA‐
40%), ‘diagnosis and what it means’ (AS‐58%, OC‐45%, EU‐56%, NA‐
51% and SA‐38%), and ‘treatment side‐effects’ (AS‐61%, OC‐44%, EU‐
45%, NA‐38% and SA‐41%). Patients also reported needing informa-
tion on ‘support for self care’, ‘psychological support’, ‘support for their
families’, and ‘fertility’ (Table 1). Only 2% of patients from AS reported
not needing any additional information compared to the other regions
(OC‐19%, EU‐11%, NA‐16% and SA‐18%) (Table 1).
Conclusion: Access to timely and credible medical information re-
mains an essential aspect of a successful patient experience and this
study shows that patients with lymphoma have diverse information
experiences and needs. It is therefore important that doctors provide
information that address(es) each patient's unique information needs.
In the future, LC would like to explore how demographic differences
may have confounded results.
Keywords: Cancer Health Disparities
Conflicts of interests pertinent to the abstract
L. Warwick
Research funding: Takeda, Pfizer and Abbvie
O. Bamigbola
Research funding: Takeda, Pfizer and Abbvie
N. Dren
Research funding: Takeda, Pfizer and Abbvie
141 | IMPACT OF DISEASE TREATMENT ON THE OUTCOME OF
PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
WITH COVID‐19: A MULTICENTER STUDY ON BEHALF OF GELLC
A. Muntañola
1
, F. Mirás
2
, J. A. Hernández‐Rivas
3
, M. Baile
4
, S.
Osorio
5
, M
a
J. Terol
6
, E. Gimeno
7
, R. Alonso
8
, P. Baltasar
9
, A. López‐
García
10
, J. Labrador
11
, J. López‐Jiménez
12
, I. Hernández‐
Rodríguez
13
, A. Alfayate
14
, A. C Oliveira
15
, M
a
I. Gómez‐Roncero
16
,
M
a
J. Vidal
17
, A. Bárez
18
, M. López‐Rubio
19
, R. Riaza
20
, J. Correa
21
, E.
Hernández‐Sánchez
22
, P. Romero
23
, L. Yáñez
24
, R. Andreu
25
, R.
Santiago
26
, A. Zabalza
27
, A. Torres
28
, C. Seri
29
, A. Ramírez‐Payer
30
,
M
a
D. García‐Malo
31
, M. García‐Pintos
32
, J. J. Mateos Mazón
33
, A.
Rodríguez‐Fernández
34
, A. M
a
Vale
35
, E. Ríos
36
, J. Loscertales
37
, J. Do
Nascimiento
38
, I. Pérez‐Fernández
39
, M
a
José Lis
40
, S. Pérez
41
, M
a
E.
Ruiz
42
, L. Villalón
43
, C. A. Velasquez
44
, F. Campoy
45
, B. Muiña
46
, J. A.
Soler
47
, M
a
J. Sánchez
48
, A. Cuesta
49
, A. Pimentel
50
, M. Sánchez‐
Ramírez
51
, I. Ruiz‐Camps
52
, G. Villacampa
52
, F. Bosch
52
, P.
Abrisqueta
52
1
Hospital Universitari Mutua Terrassa, Hematology, Barcelona, Spain,
2
Hospital Universitario 12 de Octubre, Hematology, Madrid, Spain,
3
Hospital Universitario Infanta Leonor, Hematology, Madrid, Spain,
4
Complejo Asistencial Universitario de Salamanca /IBSAL, Hematology,
Salamanca, Spain,
5
Hospital Universitario Gregorio Marañón, Hematology,
Madrid, Spain,
6
Hospital Clínico Universitario de Valencia, Hematology,
Valencia, Spain,
7
Hospital del Mar, Hematology, Barcelona, Spain,
8
Hospital Universitario Puerta de Hierro, Hematology, Madrid, Spain,
9
Hospital Universitario La Paz, Hematology, Madrid, Spain,
10
Hospital
Universitario Fundación Jiménez‐Díaz, Hematology, Madrid, Spain,
11
Hospital Universitario de Burgos, Hematology, Burgos, Spain,
12
Hospital
Ramón y Cajal, Hematology, Madrid, Spain,
13
Hospital Germans Trias i
Pujol ‐ ICO Badalona, Hematology, Barcelona, Spain,
14
Hospital Clínico
San Carlos, Hematology, Madrid, Spain,
15
Hospital Duran Reynals ‐ ICO
Hospitalet, Hematology, Barcelona, Spain,
16
Hospital Virgen de la Salud,
Hematology, Toledo, Spain,
17
Hospital Universitario de León, Hematology,
León, Spain,
18
Complejo Asistencial de Avila, Hematology, Ávila, Spain,
19
Hospital Universitario Príncipe de Asturias, Hematology, Madrid, Spain,
20
Hospital Severo Ochoa, Hematology, Madrid, Spain,
21
Hospital Clínic
Barcelona, Hematology, Barcelona, Spain,
22
Hospital Universitario de
Badajoz, Hematology, Badajoz, Spain,
23
Hospital Universitario Donostia,
Hematology, Donosti, Spain,
24
Hospital Universitario Marqués de
Valdecilla, Hematology, Santander, Spain,
25
Hospital Universitario La Fe,
Hematology, Valencia, Spain,
26
Hospital Sant Joan de Déu de Manresa‐
Fundació ALTHAIA, Hematology, Manresa, Spain,
27
Complejo
Universitario de Navarra, Hematology, Pamplona, Spain,
28
Complejo
Asistencial de Segovia, Hematology, Segovia, Spain,
29
Hospital Central de
la Defensa Gómez Ulla, Hematology, Madrid, Spain,
30
Hospital
208
-
SUPPLEMENT ABSTRACTS
Universitario Central de Asturias, Hematology, Oviedo, Spain,
31
Hospital
General Universitario Morales Meseguer, Hematology, Murcia, Spain,
32
Consorci Sanitari de Terrassa, Hematology, Terrassa, Spain,
33
Hospital
Universitario de Cruces, Hematology, Bilbao, Spain,
34
Hospital
Universitario Virgen Macarena, Hematology, Sevilla, Spain,
35
Complexo
Universitario A Coruña, Hematology, Coruña, Spain,
36
Hospital
Universitario Virgen de Valme, Hematology, Sevilla, Spain,
37
Hospital
Universitario La Princesa, Hematology, Madrid, Spain,
38
Hospital
Universitario Joan XXIII ‐ ICO Tarragona, Hematology, Tarragona, Spain,
39
Hospital Universitario Virgen de la Victoria, Hematology, Málaga, Spain,
40
Consorcio General Universitario de Valencia, Hematology, Valencia,
Spain,
41
Hospital Clínico Universitario de Valladolid, Hematology,
Valladolid, Spain,
42
Hospital Universitario del Tajo, Hematology, Aranjuez,
Madrid, Spain,
43
Hospital Universitario Fundación Alcorcón, Hematology,
Alcorcón, Madrid, Spain,
44
Hospital de Mollet, Hematology, Barcelona,
Spain,
45
Complexo Hospitalario Universitario de Ourense, Hematology,
Ourense, Spain,
46
Hospital Rafael Mendez, Hematology, Lorca, Murcia,
Spain,
47
Hospital Universitari Parc Taulí, Hematology, Sabadell, Spain,
48
Hospital Universitario Lucus Augusti, Hematology, Lugo, Spain,
49
Hospital Comarcal Sierrallana, Hematology, Torrelavega, Spain,
50
Hospital Clínico Universitario de Zaragoza, Hematology, Zaragoza,
Spain,
51
Hospital Universitario Puerto Real, Hematology, Cádiz, Spain,
52
Hospital Vall d'Hebron, Hematology, Barcelona, Spain
Introduction: Patients (pts) with CLL are at risk of more severe
COVID‐19 clinical forms and worse survival compared to general
population. Besides age and comorbidities, CLL treatments can
aggravate an immune status otherwise impaired by the disease itself,
which could also influence COVID‐19 outcome. The aim of our study
was to focus on COVID‐19 outcomes according to CLL treatment at
the time of COVID‐19.
Patients and Methods: 321 pts with CLL and COVID‐19 from 52
Spanish centers were included. Pts were classified in two cohorts
according to time of COVID. First cohort were pts from the first wave
(1W) of COVID and included 166 pts infected from March 1 to May
31, 2020; the second wave (2W) included 155 patients infected from
August 1 to January 31, 2021. Clinical characteristics, CLL treatment
status and COVID outcomes were analyzed and reported from the
whole series, and from the two cohorts separately. Finally, we
collected data referred to SARS‐CoV‐2 infection status and response,
including Polymerase Chain Reaction (PCR) negativity for COVID19
and presence of serum neutralizing antibodies.
Results: Median age was 73 years (37‐94) and 65% (n = 210) were
male. A total of 160 (50%) were on watch and wait (W&W) approach,
61 (19%) were previously treated [26 of them (43%) ended treatment
<12 months before COVID], and 100 (31%) were on active CLL
treatment at the time of COVID diagnosis (72 BTKi, 16 BCL‐2i, 9
alkylating drugs and 3 others). 1W cohort presented with more
pneumonia (87% vs. 72%, p = 0.001), supplemental oxygen re-
quirements (82% vs. 70%, p = 0.018) and admissions (92% vs 71%,
p < 0.01) than those from 2W. Conversely, no significant differences
in overall survival (OS) were found between the two cohorts.
Considering the whole series, age and D‐dimer levels were statisti-
cally associated with OS (p < 0.01). In addition, W&W patients pre-
sented better OS compared to patients on active or previous CLL
treatment finished <12 months prior COVID infection (HR 1.7 [95%
CI 1.09‐2.81], p = 0.02). Finally, median time to PCR negativity was
33 days for W&W patients compared to 55 days for treated patients
(p = 0.01) (Figure 1). Serological test was performed in 84 out of 321
cases (26%), with 47 patients (56%) becoming positive (IgG+). No
significant differences in terms of seroconversion were found ac-
cording to CLL treatment status. With a median follow‐up of 60 days
FIGURE 1 Time to PCR negativity
according to CLL status
SUPPLEMENT ABSTRACTS
-
209
(range 0‐320), no SARS‐CoV‐2 reinfections were reported and,
among IgG+ cases, none of the patients became seronegative.
Conclusions: CLL remains a high‐risk disease for COVID‐19 regard-
less of best understanding of SARS‐CoV‐2 management and
improved health‐care conditions during the 2W. Of note, patients in
W&W have better OS compared to those previously treated or in
active treatment at COVID diagnosis, suggesting that CLL treatment
is worsening COVID‐19 outcomes. Finally, PCR clears earlier in
W&W patients than in treated cases.
Keywords: Chronic Lymphocytic Leukemia (CLL)
No conflicts of interest pertinent to the abstract.
142 | DISSECTING THE GENETICS OF DIFFERENT
ANATOMICAL COMPARTMENTS OF SMALL LYMPHOCYTIC
LYMPHOMA WITH A MULTIREGIONAL SEQUENCING
APPORACH
R. Moia
1
, C. Favini
1
, V. Ferri
1
, L. Terdi Di Bergamo
2
, M. Schipani
1
, G.
Forestieri
2
, S. Sagiraju
1
, A. Andorno
3
, S. Rasi
1
, D. Talotta
1
, W. Al
Essa
1
, R. Adhinaveni
1
, A. Bruscaggin
2
, V. Spina
2
, L. De Paoli
1
, G.
Margiotta Casaluci
1
, A. Patriarca
1
, R. L. Boldorini
1
, D. Rossi
2
, G.
Gaidano
1
1
Università del Piemonte Orientale, Division of Hematology, Department of
Translational Medicine, Novara, Italy,
2
Institute of Oncology Research,
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland,
3
Università del Piemonte Orientale, Department of Pathology, Novara, Italy
Background: Small lymphocytic lymphoma (SLL) is a model that can
inform on whether spatial heterogeneity exists in leukemic B‐cell
tumors, as it is the sole entity that markedly involves both blood
and lymph nodes in all cases. Circulating tumor DNA (ctDNA) re-
capitulates disease genetics in aggressive lymphomas but its role
advantage multiregional sequencing of peripheral blood and lymph
node biopsy is unexplored.
Methods: Patients with SLL (n = 12) were referred to our institution
and provided with: i) tumour gDNA extracted from fresh frozen
lymph node cells or formalin‐fixed paraffin‐embedded (FFPE) lymph
node biopsies; ii) tumour gDNA extracted from sorted peripheral
blood (PB) CD19+/CD5+ cells; iii) ctDNA from plasma; and iv)
germline gDNA extracted from CD3+ T‐cells and/or granulocytes for
comparative purposes. The CAPP‐Seq assay was used for the muta-
tional profiling and comprised a panel of 124 genes relevant in B cell
malignancies. Copy number variants (CNVs) were identified with the
GATK4 CNV workflow.
Results: Overall, the analysis of the three SLL compartments
analyzed (i.e. lymph node biopsy, circulating PB CD19+ cell
compartment, and plasma ctDNA) identified a total of 46 mutations.
The most frequently mutated genes were TRAF3 and ASXL1in 3/12
(25.0%) patients each, followed by NOTCH1, EGR2, and SF3B1 in 2/12
(16.7%) patients each (Figure 1A). By comparing the representation
of gene mutations in the different anatomical compartments
investigated in SLL, 10/46 (21.7%) mutations were identified in all
three compartments, whereas the remaining mutations were differ-
ently distributed among the three examined compartments. More
precisely, 6/46 (13.0%) mutations were exclusive of the lymph node
biopsy, 15/46 (32.6%) were exclusive of the circulating PB CD19+
cell compartment, and only a small fraction of mutations (2/46; 4.3%)
were detectable uniquely in the plasma ctDNA (Figure 1B). Inter-
estingly, from a translational perspective, a BIRC3 mutation that may
harbor potential predictive value, has been identified only in the
circulating PB CD19+ cell compartment. In addition, a bioinformatic
algorithm for CNVs analysis has been applied to 8 patients in order to
identify potential additional differences between the lymph node
biopsy and the circulating PB CD19+ cell compartment. This algo-
rithm showed 100% concordance with FISH karyotype and allowed
the detection of at least one CNVs difference in 3/8 patients (37.5%).
Conclusions: These results suggest that the multiregional sequencing
of the different anatomical compartments of SLL is essential to gain a
comprehensive view of the disease mutational landscape. This obser-
vation may have clinical relevance when treatment tailoring is based on
specific gene mutations used as molecular predictors that might be
present in only one specific anatomical compartment of the disease.
EA – previously submitted to EHA 2021.
The research was funded by: Molecular bases of disease
dissemination in lymphoid malignancies to optimize curative thera-
peutic strategies, (5 x 1000 No. 21198), Associazione Italiana per la
Ricerca sul Cancro Foundation Milan, Italy
Keywords: Diagnostic and Prognostic Biomarkers, Chronic Lympho-
cytic Leukemia (CLL)
No conflicts of interest pertinent to the abstract.
143 | KINASE‐DEAD BRUTON'S TYROSINE KINASE (BTK)
C481F/Y MUTANTS CONFER IBRUTINIB RESISTANCE THROUGH
ACTIVATION OF HEMATOPOIETIC CELL KINASE (HCK)
K. Dhami
1
, L. W.‐K. Cheung
2
, C. Sun
3
, F. DeAnda
4
, X. Huang
1
1
Pharmacyclics LLC, an AbbVie Company, Research, Sunnyvale,
California, USA
2
Pharmacyclics LLC, an AbbVie Company, Bioinformatics,
Sunnyvale, California, USA,
3
AbbVie Inc., Research, North Chicago, Illinois,
USA,
4
Pharmacyclics LLC, an AbbVie Company, Medicinal Chemistry,
Sunnyvale, California, USA
Introduction: Ibrutinib is a once‐daily BTK inhibitor used in the
treatment of various B‐cell malignancies and chronic graft‐versus‐
host disease. Ibrutinib forms a covalent (irreversible) bond with
C481 of BTK to inhibit kinase activity and reduce downstream B‐cell
receptor (BCR) signaling. In some patients who develop resistance to
ibrutinib during treatment, acquired mutations at C481 disrupt
binding of ibrutinib to BTK. The best characterized mutation is
C481S, which results in reversible binding and decreased affinity for
ibrutinib, while retaining intact mutant BTK kinase activity. Other
clinically identified mutations are less well understood; better
210
-
SUPPLEMENT ABSTRACTS
understanding of mechanisms of BTK inhibitor resistance is impor-
tant to optimize treatment sequencing and outcomes in B‐cell ma-
lignancies. Here we characterized the novel mechanism by which 2
previously identified BTK mutations, C481F and C481Y (C481F/Y),
lead to ibrutinib resistance.
Methods: We conducted a comprehensive series of biochemical and
cellular experiments with BTK C481F, BTK C481Y, BTK C481S, and
wildtype BTK.
Results: In vitro kinase assays of purified recombinant BTK proteins
with PLCγ2 peptide substrate showed that unlike C481S, BTK
C481F/Y lacked kinase activity, with bulky F and Y sidechains steri-
cally obstructing the BTK ATP‐binding pocket in structural modeling.
Despite this, BTK C481F/Y BCR signaling remained intact with
downstream phosphorylation of PLCγ2, as well as NF‐κB nuclear
translocation in BTK
–/–
DT40 cells reconstituted with BTK C481F/Y.
BTK C481F/Y proteins were necessary to activate BCR signaling in
these cells, as BTK degradation with an established proteolysis‐
targeting chimeric molecule abrogated BCR signaling. Interestingly,
treatment with a selective HCK inhibitor, RK20449, decreased
PLCγ2 phosphorylation in a dose‐dependent manner, suggesting that
HCK is required to propagate BCR signaling with BTK C481F/Y.
Correspondingly, BTK C481F/Y immunoprecipitated with HCK when
cotransfected in HEK 293T cells and as recombinant purified pro-
teins. This interaction was dependent upon phosphorylation of Y551
of BTK C481F/Y, enabling HCK SH2 domain binding, which likely
disrupts the intramolecular autoinhibitory interaction between HCK
pY522 and the HCK SH2 domain, resulting in activation of HCK and
observed BCR signaling.
Conclusions: We characterized the novel biochemical and cellular
mechanisms of 2 acquired BTK mutations that have been associated
with the development of ibrutinib resistance in patients with B‐cell
malignancies. BTK C481F and BTK C481Y mutants provide a novel
scaffolding interaction, leading to HCK activation that facilitates
downstream BCR signaling through PLCγ2, even in the absence of
BTK kinase activity. Of current BTK inhibitors, ibrutinib uniquely
inhibits HCK activity, which may contribute to the observed dura-
bility of ibrutinib treatment efficacy.
The research was funded by: Pharmacyclics LLC, an AbbVie Company
Keywords: Molecular Targeted Therapies, Lymphoid Cancers ‐ Other
Conflicts of interests pertinent to the abstract
K. Dhami
Employment or leadership position: AbbVie
Stock ownership: AbbVie
Research funding: AbbVie
Educational grants: AbbVie
L. W.‐K. Cheung
Employment or leadership position: Pharmacyclics LLC, an AbbVie
Company
Stock ownership: AbbVie, Eli Lilly
Other remuneration: Patents, royalties, and other intellectual prop-
erty: Pharmacyclics LLC, an AbbVie Company
C. Sun
Employment or leadership position: AbbVie
Stock ownership: AbbVie
F. DeAnda
Employment or leadership position: AbbVie
Other remuneration: Patents, royalties, and other intellectual prop-
erty: Pharmacyclics LLC, an AbbVie Company
X. Huang
Employment or leadership position: Pharmacyclics, An AbbVie
Company
Stock ownership: AbbVie, Sutro Biopharma
MANTLE CELL LYMPHOMA
144 | CURRENT ROLE OF ALLOGENEIC STEM CELL
TRANSPLANTATION IN MANTLE CELL LYMPHOMA IN THE ERA
OF NEW IMMUNOTHERAPEUTIC AND TARGETED THERAPIES.
THE GETH/GELTAMO EXPERIENCE
A. Gutierrez
1
, L. Bento
1
, S. Novelli
2
, G. Gutierrez
3
, Q. Salas
3
, M.
Bastos‐Oreiro
4
, A. Perez
5
, R. Hernani
5
, M. C. Viguria
6
, O. Lopez‐
Godino
7
, J. Montoro
8
, J. L. Piñana
8
, C. Ferra
9
, R. Parody
10
, C. Mar-
tin
11
, J. Gomez‐Espuch
12
, L. Yañez
13
, G. Rodriguez
14
, J. Zanabilli
15
, P.
Herrera
16
, M. R. Varela
17
, A. Sampol
1
, M. D. Caballero
18
1
Hospital Universitario Son Espases, Hematology, 07120, Spain,
2
Hospital
Sant Pau, Hematology, Barcelona, Spain,
3
Hospital Clinic, Hematology,
Barcelona, Spain,
4
Hospital Gregorio Marañon, Hematology, Madrid,
Spain,
5
Hospital Clinico Universitario de Valencia, Hematology, Valencia,
Spain,
6
Hospital de Navarra, Hematology, Pamplona, Spain,
7
Hospital
Morales Meseguer, Hematology, Murcia, Spain,
8
Hospital La Fe,
Hematology, Valencia, Spain,
9
Hospital de Can Ruti, Hematology,
Badalona, Spain,
10
Hospital de Bellvitge, Hematologyi, Barcelona, Spain,
11
Hospital Reina Sofia, Hematology, Cordoba, Spain,
12
Hospital de la
Arrixaca, Hematology, Murcia, Spain,
13
Hospital de Valldecilla,
Hematology, Santander, Spain,
14
Hospital Virgen del Rocio, Hematology,
Sevilla, Spain,
15
Hospital Universitario Central de Asturias, Hematology,
Oviedo, Spain,
16
Hospital Ramon y Cajal, Hematology, Madrid, Spain,
17
Hospital Juan Canelejo, Hematology, La Coruña, Spain,
18
Hospital de
Salamanca, Hematology, Salamanca, Spain
Introduction: Mantle cell lymphoma (MCL) has been associated with
poor prognosis, chemorefractoriness and older median age at diag-
nosis. For transplant‐eligible patients, clinical outcome improves us-
ing intensive cytarabine‐based induction, followed by autologous
stem cell transplant (ASCT). Recently, new approaches with anti‐
CD20 maintenance, new target drugs or new ways of immuno-
therapy such as CARTs are changing the therapeutic landscape.
Allogeneic Stem Cell Transplantation (Allo‐SCT) is a curative option
for selected patients but with significant non‐relapse mortality
(NRM). Our objective was to analyze long‐term results in patients
receiving allo‐SCT in Spain.
SUPPLEMENT ABSTRACTS
-
211
Methods: We performed a retrospective multicenter study including
patients from centers of GETH/GELTAMO with relapsed/refractory
(R/R) MCL treated with allo‐SCT from March 1995 to February 2020.
The primary endpoints were event‐free survival (EFS), overall survival
(OS), NRM and cumulative incidence (CI) of relapse and graft versus
host disease (GVHD).
Results: We included one‐hundred and thirty‐five patients with R/R
MCL that fulfilled the inclusion criteria (Table 1). Median age was 56
years (27% >60 years); 49% had previous ASCT and median number
of previous lines of therapy were 2 (1‐8). Disease status at allo‐SCT
was complete response (CR) in 64%, partial response (PR) in 26% and
stable/progressive disease (SD/PD) in 10%. Most patients (85%)
received reduced intensity conditioning (RIC). After a median follow‐
up of 68 months (2‐247), 5‐year EFS and OS were 47% and 50%.
NRM at day 100 and 5 years were 20% and 44%, respectively.
Overall and CR rates on day 100 were 86% and 80%, respectively.
The main causes of death were secondary to NRM: 32% GVHD, 32%
infection, 3% veno‐oclussive disease (VOD), 3% thrombotic micro-
angiopathy and 15% others. Progression was the cause of death in
only 14%. CI of relapse at 1 and 5 years were 9% and 16%, respec-
tively. CI of grade 3‐4 acute GVHD (aGVHD) at day 100 and mod-
erate/severe chronic GVHD at 5 years were 29% and 42%,
respectively. In the multivariate analysis we found the following in-
dependent factors: ECOG PS > 1 (HR 3.2; p = 0.017) and donor
mismatch (HR 2.2; p = 0.007) for EFS; ECOG PS > 1 (HR 3.1; p =
0.018) and previous ASCT (HR 2.1; p = 0.004) for OS; and grade 3‐4
aGVHD (RR 7.1; p < 0.001) for NRM.
Conclusions: Our data confirmed that allo‐SCT may be a curative
option in R/R MCL with low CI of relapse, although NRM is still high,
mainly secondary to aGVHD. Results are better for fit patients, using
HLA‐identical donor (related or unrelated) and without previous
ASCT. However, in the era of new immunotherapy and target drugs,
allo‐SCT should only be considered in selected patients failing these
new approaches.
EA – previously submitted to EHA 2021.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Stem Cell
Transplant
No conflicts of interest pertinent to the abstract.
145 | ATEZOLIZUMAB + OBINUTUZUMAB + VENETOCLAX
IN PATIENTS WITH RELAPSED OR REFRACTORY MARGINAL
ZONE LYMPHOMA: PRIMARY ANALYSIS OF A PHASE 2 TRIAL
FROM LYSA
C. Herbaux
1
, J. M. Schiano de Colella
2
, C. Thieblemont
3
, S. Guidez
4
,
L. Ysebaert
5
, H. Tilly
6
, S. Le Gouill
7
, R. Houot
8
, E. Bachy
9
, C. Laurent
10
,
TABLE 1 Characteristics of patients
212
-
SUPPLEMENT ABSTRACTS
G. Damaj
11
, P. Feugier
12
, N. Morineau
13
, K. Tarte
14
, F.
Morschhauser
15
, G. Cartron
1
1
CHU Montpellier, Hématologie Clinique, Montpellier, France,
2
IPC,
Hematology, Marseille, France,
3
St Louis, Hematology, Paris, France,
4
CHU, Hematology, Poitiers, France,
5
Oncopole, Hematology, Toulouse,
France,
6
CHB Unicancer, Hematology, Rouen, France,
7
CHU, Hematology,
Nantes, France
8
CHU, Hematology, Rennes, France,
9
CHU, Hematology,
Lyon, France,
10
Oncopole, Pathology, Toulouse, France,
11
CHU,
Hematology, Caen, France,
12
CHU, Hematology, Nancy, France,
13
CHD
Vendée, Hematology, La Roche sur Yon, France,
14
CHU, Pathology,
Rennes, France,
15
CHU, Hematology, Lille, France
Introduction: Relapsed and refractory (R/R) Marginal Zone Lym-
phomas (MZL) treatment remains challenging. Atezolizumab (ATE)
and obinutuzumab (OBI) are monoclonal antibodies acting respec-
tively to inhibit T‐lymphocyte exhaustion or by inducing lymphoma
cells cytotoxicity, whereas venetoclax (VEN) is a small molecule
inhibiting BCL‐2. Combining tumor‐targeted therapies with agents
that enhance anti‐tumor immunity represents an attractive treat-
ment paradigm. This LYSA sponsored multicenter phase 2 trial
(NCT03276468) evaluated ATE, OBI and VEN combination in R/R B‐
cell lymphomas. Herein, we present primary efficacy and safety data
from the MZL cohort.
Methods: Patients ≥18 years with biopsy‐confirmed R/R MZL who
failed at least one line of therapy were eligible. OBI was given IV at
1 g on day (D) 1, 8 and 15 of cycle (C) 1 and on D1 from C2 to C8
every 3 weeks. ATE was given IV, 1.2 g every 3 weeks, started at D2
of C1, then administered at D2 of each cycle for 24 cycles. VEN was
given orally at 800 mg/D at full dose, starting on D8C1 for 24 cycles.
The primary endpoint was the Overall Response Rate (ORR) evalu-
ated by Cheson criteria (CT scan) at the end of induction (EOI) after
8 cycles of ATE, OBI and VEN (M6) or at premature treatment
discontinuation.
Results: At the time of the primary analysis (08 Jan 2021), 20 MZL
patients were enrolled, including 13 nodal MZL, 5 extra‐nodal MZL
(MALT) and 2 splenic MZL. The median follow‐up was 11.9 months
[0.7‐23.6]. Thirteen patients completed induction phase and 11 pa-
tients started maintenance. Baseline characteristics were: median
age, 69 years (52‐83); male, 55.6%; Ann Arbor Stage IV, 100%; bone
marrow infiltration, 38.9%; ≥ 2 extra‐nodal sites, 50%; >2 prior lines
of therapy, 22.2%; refractory to last line of prior regimen, 33.3%. The
ORR at EOI was measured at 66.76% [44.6%‐84.4%], including 16.7%
of CR and 50.0% PR. Best of radiological response rate (BOR) was
77.8% [56.1%‐92.0%] including 22.2% of CR. To date, these re-
sponses seem durable with only 3 reported relapses. Eleven patients
(55%) received the full induction treatment. At the time of analysis, a
median of 8 cycles [1‐8] has been administered. A total of 14 (70%)
pts experienced grade 3–4 adverse event (AE) and no patient expe-
rience an AE that led to discontinuation of any drug. AE of grade 3 or
more reported in at least 10% of patients were neutropenia (55.0%),
thrombocytopenia (20.0%) and anemia (10.0%). Of note, no patient
experienced immune‐related disorder during induction.
Conclusion: ATE, OBI and VEN combo appears to be well tolerated,
with no unexpected toxicity brought by the combination. The ORR at
EOI seems to be comparable to other innovative regiments in this
setting, with durable responses to date.
The research was funded by: Roche, Abbvie
Keywords: Extranodal non‐Hodgkin lymphoma, Indolent non‐
Hodgkin lymphoma, Combination Therapies
Conflicts of interests pertinent to the abstract
C. Herbaux
Consultant or advisory role: Roche, Abbvie
Honoraria: Roche, Abbvie
Educational grants: Roche, Abbvie
146 | ACALABRUTINIB MONOTHERAPY IN PATIENTS WITH
RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA: FINAL
RESULTS FROM A PHASE 2 STUDY
M. Wang
1
, S. Rule
2
, P. L. Zinzani
3
, A. Goy
4
, O. Casasnovas
5
, S. D.
Smith
6
, G. Damaj
7
, J. K. Doorduijn
8
, T. Lamy
9
, F. Morschhauser
10
, C.
Panizo
11
, B. Shah
12
, A. Davies
13
, R. Eek
14
, J. Dupuis
15
, E. Jacobsen
16
,
A. P. Kater
17
, S. Le Gouill
18
, L. Oberic
19
, T. Robak
20
, P. Jain
21
, R.
Calvo
22
, L. Tao
23
, M. Dlugosz‐Danecka
24
1
MD Anderson Cancer Center, University of Texas, Lymphoma ‐ Myeloma,
Division of Cancer Medicine, Houston, Texas, USA,
2
Plymouth University
Medical School, Hematology, Plymouth, UK,
3
Institute of Hematology
“Seràgnoli” University of Bologna, Experimental, Diagnostic and Specialty
Medicine ‐ DIMES, Bologna, Italy,
4
John Theurer Cancer Center,
Hackensack University Medical Center, Oncology, Hackensack, New
Jersey, USA,
5
CHU Dijon ‐ Hôpital d’Enfants, Hematology, Dijon, France,
6
Fred Hutchinson Cancer Research Center, University of Washington,
Medical Oncology, Seattle, Washington, USA,
7
Institut d’Hématologie de
Basse‐Normandie, Hematology, Caen, France,
8
Erasmus MC, HOVON
Lunenburg Lymphoma Phase I/II Consortium, Hematology, Rotterdam,
Netherlands,
9
CHU de Rennes, Hematology, Rennes, France,
10
CHU Lille,
ULR 7365 ‐ GRITA ‐ Groupe de Recherche sur les formes Injectables et les
Technologies Associées , Hematology, Lille, France,
11
Clínica Universidad
de Navarra, Hematology, Pamplona, Spain,
12
Moffitt Cancer Center,
Malignant Hematology, Tampa, Florida, USA,
13
Cancer Research UK
Experimental Cancer Medicines Centre, University of Southampton Fac-
ulty of Medicine, Medical Oncology, Southampton, UK,
14
Border Medical
Oncology, Medical Oncology, Albury, Australia,
15
Unité Hémopathies
Lymphoïdes, AP‐HP Hôpital Henri Mondor, Hematology, Créteil, France,
16
Dana Farber Cancer Institute, Harvard Medical School, Medical
Oncology, Boston, Massachusetts, USA,
17
Amsterdam University Medical
Center, Amsterdam, on behalf of Hovon, Hematology, Lymphoma and
Myeloma Research , Amsterdam, Netherlands,
18
CHU de Nantes—Hotel
Dieu, Hematology, Nantes, France,
19
Institut Universitaire du Cancer—
Oncopole Toulouse (IUCT‐O), Hematology, Toulouse, France,
20
Coperni-
cus Memorial Hospital, Medical University of Lodz, Hematology, Lodz,
SUPPLEMENT ABSTRACTS
-
213
Poland,
21
MD Anderson Cancer Center, University of Texas, Leukemia,
Houston, Texas, USA,
22
AstraZeneca, Clinical Development Hematology,
R&D Oncology, Gaithersburg, Maryland, USA,
23
AstraZeneca, Biostatis-
tics, South San Francisco, California, USA,
24
Maria Sklodowska‐Curie
National Research Institute of Oncology, Hematology, Krakow, Poland
Introduction: Acalabrutinib is a next‐generation Bruton tyrosine ki-
nase (BTK) inhibitor approved in relapsed/refractory (R/R) mantle
cell lymphoma (MCL). Initial results demonstrated efficacy and safety
of acalabrutinib in R/R MCL in a single‐arm phase 2 study (ACE‐LY‐
004; NCT02213926) (Wang M, et al. Leukemia. 2019;33:2762‐6). In a
long‐term analysis at 3‐year follow‐up, safety and efficacy of
acalabrutinibwere consistent and median overall survival (OS)
had not yet been reached (Wang M, et al. Blood. 2020;136(Suppl
1):38‐9). Here, we present final study results, including updated OS
data.
Methods: Adults with R/R MCL (with no prior BTK/BCL‐2 inhibitor
exposure) received oral acalabrutinib 100 mg twice daily until pro-
gressive disease (PD) or toxicity. Overall response rate (ORR;
investigator‐assessed partial response [PR] or better per Lugano
classification), duration of response (DOR), progression‐free survival
(PFS), OS, and safety were assessed.
Results: A total of 124 patients were included (median age, 68
[range: 42–90] y; Eastern Cooperative Oncology Group performance
status ≤1, 93%; extranodal involvement, 72%; intermediate‐/high‐
risk simplified MCL International Prognostic Index score, 44%/17%;
median number of prior therapies, 2 [range: 1–5]). After a median
follow‐up of 38.1 months at a December 4, 2020 data cutoff for the
final analysis, reported ORR and complete response (CR) were un-
changed since the previous report (81% and 48%). Median DOR and
median PFS also remained unchanged (29 months and 22 months).
At the final data cutoff, median OS was reached at 59.2 months (95%
CI: 36.5, not evaluable; Figure). The adverse‐event (AE) profile
remained consistent with the known acalabrutinib safety profile,
with the most common AEs (≥20%) being headache (38.7%), diarrhea
(37.9%), fatigue (29.8%), cough (23.4%), myalgia (21.8%), and nausea
(21.8%). Select AEs of interest included atrial fibrillation (any grade,
n = 3 [2.4%]; grade 3/4, n = 0), hypertension (any grade, n = 5 [4.0%];
grade 3/4, n = 2 [1.6%]), hemorrhage (any grade, n = 46 [37.1%];
grade 3/4, n = 5 [4.0%]), and infections (any grade, n = 84 [67.7%];
grade 3/4, n = 21 [16.9% ]). At the data cutoff, 18 patients remained
on treatment and the median treatment exposure was 17.5 months
(range: 0.1–65.3). Treatment discontinuations due to disease pro-
gression occurred in 77 patients (62.1%) and those due to AEs
occurred in 15 patients (12.1%). Of the 59 deaths (47.6%) reported
at the time of data cutoff, 40 (32.3%) were due to disease progres-
sion and 6 (4.8%) were due to AEs.
Conclusions: Long‐term 3.5‐year median follow‐up from this study
confirmed that acalabrutinib is highly active at a median time on
treatment of 17.5 months. This study reports that median OS has
been reached at 59 months for patients with R/R MCL receiving
acalabrutinib treatment.
The research was funded by: Acerta Pharm, a member of the
AstraZeneca group
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Molecular
Targeted Therapies
Conflicts of interests pertinent to the abstract
M. Wang
Consultant or advisory role: – InnoCare, Loxo Oncology, Juno, Onc-
ternal, CStone, AstraZeneca, Janssen, VelosBio, Pharmacyclics,
Genentech, Bayer Healthcare
Honoraria: Janssen, Acerta Pharma, OMI, Physicians Education
Resources, Dava Oncology, CAHON, Hebei Cancer Prevention
Federation, Clinical Care Options, Mumbai Hematology Group,
Anticancer Association
Research funding: Pharmacyclics, Janssen, AstraZeneca, Celgene,
Loxo Oncology, Kite Pharma, Juno, BioInvent, VelosBio, Acerta
Pharma, Oncternal, Verastem, Molecular Templates, Lilly, Innocare
Educational grants: Pharmacyclics, Janssen, AstraZeneca, Celgene,
OMI, Kite Pharma
S. Rule
Consultant or advisory role: AstraZeneca, Celgene, Celltrion, Janssen
Oncology, Roche Pharma AG, VelosBio
Research funding: Janssen Oncology, Roche Pharma AG.
Other remuneration: Speakers Bureau – Janssen Oncology.
P. L. Zinzani
Consultant or advisory role: Verastem, Celltrion, Gilead, Janseen‐
Cilag, BMS, Servier, Sandoz, MSD, TG Therapeutics, Takeda, Roche,
Eusapharma, Kwoya Kirin, Sanofi, ADC Therapteutics
Other remuneration: Speakers’ Bureau ‐ Verastem, Celltrion, Gilead,
Janseen‐Cilag, BMS, Servier, MSD, TG Therapeutics, Takeda, Roche,
Eusapharma, Kyowa Kirin
A. Goy
Employment or leadership position: RCCA/OMI, AstraZeneca,
Acerta, COTA, Kite Pharma, Janssen
Consultant or advisory role: PracticeUpdate Oncology, Xcenda,
Honoraria: Celgene
Research funding: Hackensack UMC and University of Nebraska, Kite
Pharma, Janssen, Celgene, AstraZeneca, Acerta, Bayer, CALBG,
Constellation, Genentech/Roche, Infinity, Karyopharm, Morphosys,
AbbVie, MD Anderson, Verastem
O. Casasnovas
Consultant or advisory role: AbbVie, Merck Sharp & Dohme, Amgen
Honoraria: AbbVie, Merck Sharp & Dohme, Amgen
Research funding: Roche, Gilead, Takeda
Educational grants: Roche, Gilead, Takeda
S. D. Smith
Consultant or advisory role: AstraZeneca, Millenium/Takeda, Bei-
gene, Karyopharm, Kite Pharma
214
-
SUPPLEMENT ABSTRACTS
Research funding: Acerta Pharma BV, AstraZeneca, Bayer, Ayala,
Bristol Meyers Squibb, De Novo Biopharma, Genentech, Ignyta,
Incyte, Merck, Pharmacyclics, Portola, Seattle Genetics
G. Damaj
Consultant or advisory role: Roche, Takeda
Educational grants: AbbVie, Pfizer, Roche
J. K. Doorduijn
Educational grants: Roche
F. Morschhauser
Consultant or advisory role: AbbVie, Celgene, Epizyme, F. Hoffmann‐
La Roche, Gilead, Genentech, Servier
Other remuneration: Speakers Bureau – F. Hoffmann‐La Roche,
Gilead
C. Panizo
Employment or leadership position: Clínica Universidad de Navarra
Consultant or advisory role: Janssen, Roche
SUPPLEMENT ABSTRACTS
-
215
Other remuneration: Speakers Bureau – Bristol Myers Squibb,
Kyowa Kirin
B. Shah
Employment or leadership position: Moffitt Cancer Center
Consultant or advisory role: NCCN: Vice‐Chair, Acute Lymphoblastic
Leukemia Working Group
Honoraria: Kite Pharma, Gilead, Celgene, Juno, Bristol Meyers
Squibb, Novartis, Pfizer, Amgen, Spectrum, Acrotech, Precision
Biosciences, Beigene, AstraZeneca, Pharmacyclics, Jansen, Adaptive
Research funding: Kite Pharma, Gilead, Jazz, Incyte
Educational grants: Kite Pharma, Gilead, Precision Biosciences,
Novartis, AstraZeneca
A. Davies
Consultant or advisory role: Roche, Celgene, Gilead/Kite Pharma,
Acerta, Karyopharma, Regeneron, Incyte, Takeda, VelosBio, Mor-
phoSys AG
Honoraria: Roche, Celgene, Gilead/Kite Pharma, Takeda, MorphoSys
AG, Janssen, Karyopharma
Research funding: Roche, Acerta Pharma, AstraZeneca, Celgene,
Gilead/Kite Pharma, ADC Therapeutics, Janssen, Takeda,
Karyopharma
Educational grants: Roche, Takeda
J. Dupuis
Employment or leadership position: Henri Mondor University Hos-
pital Creteil France
Consultant or advisory role: AstraZeneca
E. Jacobsen
Consultant or advisory role: Acerta, AstraZeneca, Merck
Honoraria: Takeda
Research funding: Merck, Pharmacyclics, F. Hoffmann‐LaRoche,
Novartis
A. P. Kater
Research funding: Janssen, Celgene, Genentech, AbbVie, Roche
S. Le Gouill
Consultant or advisory role: Loxo Oncology
Honoraria: Roche, Genentech, Janssen‐Cilag, Abbvie, Celgene, Jazz,
Kite Pharma, Loxo, Daiichi‐Sankyo, Servier
L. Oberic
Consultant or advisory role: Roche, Janssen
Honoraria: Roche
Educational grants: Roche, Janssen
T. Robak
Employment or leadership position: Medical University of Lodz.
Consultant or advisory role: Sandoz, Takeda, Momenta
Research funding: Acerta, Roche, Janssen, AbbVie, Novartis, Bio-
Gene, AstraZeneca, Pharmacyclics, UCB, Pfizer, Morphosys, UTX‐
TGR, GSK, Bristol Myers Squibb
Educational grants: Roche, Janssen, AbbVie. Honoraria – Sandoz,
UCB, Novartis, Octapharma, BioGene, AstraZeneca, Pharmacyclics
R. Calvo
Employment or leadership position: AstraZeneca
Stock ownership: AstraZeneca
L. Tao
Employment or leadership position: AstraZeneca, Clindata Insight
147 | TIME TO SECOND LINE BRUTON TYROSINE KINASE
THERAPY AND AGE AT ITS INITIATION ARE STRONGLY
ASSOCIATED WITH SUBSEQUENT OVERALL SURVIVAL IN
PATIENTS WITH FIRST RELAPSE OF MANTLE CELL LYMPHOMA
D. Villa
1
, A. Jiang
1
, N. Crosbie
2
, S. Rule
2
, R. McCulloch
2
, C. Visco
3
, M.
J. Buege
4
, A. Kumar
5
, D. Bond
6
, J. Paludo
7
, M. J. Maurer
8
, G.
Thanarajasingam
7
, J. Baech
9
, T. El‐Galaly
9
, L. Kugathasan
1
, A. S.
Gerrie
1
, D. Lewis
2
1
BC Cancer, Centre for Lymphoid Cancer, Vancouver, Canada,
2
University
Hospitals Plymouth NHS Trust, Haematology, Plymouth, UK,
3
University
of Verona, Hematology, Verona, Italy,
4
Memorial Sloan Kettering Cancer
Center, Clinical Pharmacy, Lymphoma, New York, USA,
5
Memorial Sloan
Kettering Cancer Center, Division of Hematologic Malignancies, New York,
USA,
6
The Ohio State University, Hematology, Columbus, USA,
7
Mayo
Clinic, Hematology, Rochester, USA,
8
Mayo Clinic, Division of Clinical
Trials and Biostatistics, Rochester, USA,
9
Aalborg University Hospital,
Haematology, Aalborg, Denmark
Introduction: Time to disease progression after first line (1L) therapy
is a robust prognostic factor in mantle cell lymphoma (MCL), although
studies have included a broad range of 1L, second (2L) and subse-
quent lines of therapy. Whilst the majority of patients respond to
Bruton tyrosine kinase inhibitors (BTKi), relapse is inevitable and it is
important to understand prognostic factors of response to 2L BTKi
which may allow planning of subsequent therapy such as chimeric
antigen receptor T‐cell (CART) therapy.
Methods: Patients ≥18 years at diagnosis of MCL were included if
they were treated with (a) any 1L rituximab‐containing chemo-
therapy regimen and (b) any 2L single‐agent BTKi. OS2 was defined
from initiation of 2L BTKi until death from any cause or censoring at
last follow‐up. The association between age at 2L BTKi, time to 2L
BTKi, and OS2 was analyzed using Cox proportional hazards models
and spline‐based associations. The final model was validated in an
independent cohort of 200 patients with relapsed/refractory (R/R)
MCL uniformly treated with 2L ibrutinib from a national audit
database from the UK National Health System. Model performance
was assessed via time‐dependent concordant indices and calibration
curves.
Results: A total of 154 patients were identified from 6 international
centers. Median age at 2L BTKi was 69 years (range 22‐91). Median
216
-
SUPPLEMENT ABSTRACTS
time from initiation of 1L to 2L therapy was 25 months (range 1‐131).
BTKi were ibrutinib (86%), acalabrutinib (13%), zanubrutinib (1%).
Mean duration of 2L BTKi was 12 months (range 1 – 72). At data cut‐
off, 111 (72%) had discontinued BTKi: 79% progression, 13% toxicity,
4% allotransplant, 3% solid cancer, 1% noncompliance.
The median OS2 was 2.7 years (95% CI 1.9‐5.6) and the 2‐year
OS2 was 56% (95% CI 48‐66). In univariable analyses, time to 2L
BTKi was strongly associated with OS2 (spline p < 0.001). Age at 2L
BTKi as a linear term was also associated with OS2 (p < 0.001). In a
model including both variables, age at 2L BTKi (p = 0.015) and time
to 2L BTKi (p < 0.001) remained significant. C‐index was 0.72 at 2
years, and the model was well calibrated (predicted 2‐year OS2 55%).
A nomogram to predict 2‐year OS2 was constructed (Figure 1).
In the validation cohort, median age at 2L ibrutinib was 71 years
(range 33‐94), and median time to 2L ibrutinib was 24 months (range
1‐158). Median OS2 was 1.8 years (95% CI 1.4‐3.1) and 2‐year OS2
was 48% (95% CI 40‐57%). The mean prediction for 2‐year OS2 in
the validation data set was 54%. C‐index was 0.64 at 2 years.
Conclusions: Time to 2L BTKi and age at its initiation are strongly
associated with OS2 in R/R MCL. A simple model incorporating these
two variables is clinically useful to predict outcomes with 2L BTKi
and plan subsequent therapy such as CART. Recalibration of the
model in a younger/fitter population, or with additional variables
such as MIPI, blastoid morphology, TP53, and Ki67 is ongoing and
may provide more reliable OS2 estimates.
Keywords: Diagnostic and Prognostic Biomarkers, Indolent non‐
Hodgkin lymphoma, Molecular Targeted Therapies
Conflicts of interests pertinent to the abstract
D. Villa
Honoraria: Janssen, AstraZeneca, Kite/Gilead
Research funding: AstraZeneca (institution)
M. J. Maurer
Consultant or advisory role: Pfizer, Kite, Morphosys
Research funding: BMS, Genentech, Nanostring, Morphosys
A. S. Gerrie
Consultant or advisory role: Janssen, AbbVie, Celgene, Sandoz,
AstraZeneca, BMS
Honoraria: Janssen, AbbVie, AstraZeneca
Research funding: Janssen, Roche, Abbvie, AstraZeneca (all to
institution)
148 | SURVIVAL FOLLOWING FIRST RELAPSE IN YOUNGER
PATIENTS WITH MANTLE CELL LYMPHOMA
R. Karmali
1
, A. Donovan
2
, N. Wagner‐Johntson
3
, M. Messmer
3
, A.
Mehta
4
, J. K. Anderson
4
, N. Reddy
5
, A. E. Kovach
5
, D. J. Landsburg
6
,
M. Glenn
7
, D. J. Inwards
8
, K. Ristow
8
, F. Lansigan
2
, J. B. Kaplan
1
, P. B.
Caimi
9
, S. Rajguru
10
, A. Evens
11
, A. Klein
12
, E. Umyarova
13
, J. E.
Amengual
14
, J. K. Lue
14
, C. Diefenbach
15
, N. Epperla
16
, S. K. Barta
6
, F.
J Hernandez‐Ilizaliturri
17
, E. Handorf
18
, D. Villa
19
, A. S. Gerrie
19
, S.
Li
20
, J. Mederios
20
, M. Wang
20
, J. Cohen
21
, O. Calzada
21
, M. Chur-
netski
21
, B. Hill
22
, Y. Sawalha
22
, J. N. Gerson
6
, S. Kothari
17
, J. M.
Vose
23
, M. Bast
23
, T. S. Fenske
24
, S. Narayana Rao Gari
24
, K. J.
Maddocks
16
, D. Bond
16
, V. Bachanova
25
, B. Kolla
25
, J. Chavez
26
, B.
Shah
26
1
Northwestern, Hem Onc, Evanston, USA,
2
Dartmouth Hitchcock, Hem
Onc, Lebanon, USA,
3
Johns Hopkins University, Hem Onc, Baltimore, USA,
4
University of Alabama Cancer Center, Hem Onc, Birmingham, USA,
5
Vanderbilt Ingram Cancer Center, Hem Onc, Nashville, USA,
6
University
of Pennsylvania, Hematology Oncology, Philadelphia, Pennsylvania, USA,
7
Huntsman Cancer Institute, Hem Onc, Salt Lake City , USA,
8
Mayo Clinic,
Hem Onc, Rotchester, USA,
9
Case Western Reserve University, Hem
Onc, Cleveland, USA,
10
University of Wisconsin, Hem Onc, Madison,
USA,
11
Rutgers, Hem Onc, New Brunswick, USA,
12
Tufts, Hem Onc,
Boston, USA,
13
University of Vermont, Hem Onc, Burlington, USA,
14
Columbia, Hem Onc, New York, USA,
15
New York University, Hem Onc,
New York, USA,
16
Ohio State University, Hem Onc, Columbus, USA,
17
Roswell Park, Hem Onc, Buffalo, USA,
18
Fox Chase Cancer Center,
Hematology Oncology, Philadelphia, USA,
19
BC Cancer, Hem Onc,
Vancouver, Canada,
20
MD Anderson, Hem Onc, Houstin, USA,
21
Emory,
Hem Onc, Atlanta, USA,
22
CCF, Hem Onc, Cleveland, USA,
23
University of
Nebraska Cancer Center, Hem Onc, Omaha, USA,
24
Medical College of
Wisconsin, Hem Onc, Milwaukee , USA,
25
University of Minnesota ,
Hem Onc, Minneapolis, USA,
26
Moffitt Cancer Center, Hem Onc,
Tampa, USA
SUPPLEMENT ABSTRACTS
-
217
Introduction: Mantle cell lymphoma (MCL) is an incurable B‐cell non‐
Hodgkin lymphoma. Though most patients achieve remission
following induction therapy, relapse is inevitable. We previously
described the outcome following upfront treatment of a cohort of
1029 patients with MCL aged £65 years and transplant eligible.
Herein we report survival outcomes following first relapse in the
same cohort.
Methods: This multi‐center retrospective study included adults with
newly diagnosed MCL treated with induction chemotherapy between
2000‐2015. Twenty‐five US and Canadian academic medical centers
participated in the study. The primary objective was to assess post‐
relapse overall survival (PROS). Secondary objectives included
assessment of the impact on survival of autologous hematopoietic
cell transplant (AHCT) in first remission and of time period of relapse
(2000‐2006, era‐1 vs 2007‐2015, era‐2). PROS was analysed using
Kaplan‐Meier and Cox proportional hazards regression models.
Results: Of the 1029 MCL patients who met the inclusion criteria,
657 (64%) underwent AHCT in first remission; 372 (36%) did not.
With a median follow up of 6.3 years (range 1 month‐17.1 years), 510
patients (50%) progressed, with 281 (27%) having progression of
disease at 2 years (POD24). Among the patients who received AHCT,
281 (43%) progressed, compared with 229 (62%) who did not receive
AHCT. Following progression, 267 patients died by last follow up and
the median PROS was 39 months. PROS did not differ based on
receipt of AHCT, with a median PROS of 33 months for those who
received AHCT versus 42 months for those did not (p = 0.6). There
was no difference in PROS based on era of relapse regardless of
receipt of AHCT (era‐1, no AHCT: median 71 mo; era‐1, AHCT:
median 156 mo; era‐2, no AHCT: median 99 mo; era‐2, AHCT: me-
dian: 91 mo; p = 0.54) (Figure 1).
Conclusion: Median overall survival following first relapse in
young and fit MCL patients treated with induction chemotherapy is
3.25 years. Receipt of prior AHCT following induction therapy and
era of relapse had no significant impact on PROS. The absence of
difference in PROS based on AHCT may be attributable to the
availability of targeted agents, which may be equally effective
regardless of resistance to cytotoxic therapy. These data provide a
benchmark to compare outcomes following CD19 directed chimeric
antigen receptor T‐cells for patients with MCL in the relapse setting.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Indolent non‐
Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
F. Lansigan
Consultant or advisory role: Celgene, Curis, MorphoSys
Honoraria: Seattle Genetics
Research funding: Takeda, Triphase Accelerator, Curis
S. K. Barta
Consultant or advisory role: Takeda, Merck, Bayer, Celgene, and
Seattle Genetics
Honoraria: Seattle Genetics, Mundipharma, and Monsanto
A. S. Gerrie
Consultant or advisory role: Janssen, AbbVie, Celgene, Sandoz,
Astrazeneca, BMS
Honoraria: Janssen, AbbVie, Astrazeneca
Research funding: Janssen, Roche, AbbVie, Astrazeneca
M. Wang
Consultant or advisory role: InnoCare, Loxo Oncology, Juno, Onc-
ternal, CStone, AstraZeneca, Janssen, VelosBio, Pharmacyclics,
Genentech, Bayer Healthcare
Honoraria: Janssen, Acerta Pharma, OMI, Physicians Education Re-
sources, Dava Oncology, CAHON, Hebei Cancer Prevention Feder-
ation, Clinical Care Options, Mumbai Hematology Group, Anticancer
Association
Research funding: Pharmacyclics, Janssen, AstraZeneca, Celgene,
Loxo Oncology, Kite Pharma, Juno, BioInvent, VelosBio, Acerta
Pharma, Oncternal, Verastem, Molecular Templates, Lilly, Innocare
Other remuneration: Pharmacyclics, Janssen, AstraZeneca, Celgene,
OMI, Kite Pharma
J. N. Gerson
Consultant or advisory role: Pharmacyclics, Genentech, TG
Therapeutics
Research funding: LOXO
D. Bond
Consultant or advisory role: Seattle Genetics
149 | ROLE OF MAINTENANCE RITUXIMAB AFTER FIRST‐LINE
BENDAMUSTINE + RITUXIMAB OR R‐CHOP IN PATIENTS WITH
MANTLE CELL LYMPHOMA FROM A LARGE US REAL‐WORLD
COHORT
M. Wang
1
, G. Salles
2
, A. Kumar
3
, K. Qi
4
, K. Daly
5
, L. Parisi
6
, A. Zhu
7
,
P. Martin
8
1
The University of Texas MD Anderson Cancer Center, Department of
Lymphoma/Myeloma, Houston, Texas, USA,
2
Memorial Sloan Kettering
Cancer Center, Lymphoma Service at the Department of Medicine, New
FIGURE 1 Overall survival after progression based on era of
relapse and receipt of AHCT
218
-
SUPPLEMENT ABSTRACTS
York, USA,
3
Memorial Sloan Kettering Cancer Center, Lymphoma Service
at the Department of Medicine, New York, USA,
4
Janssen Research &
Development, IHI RWE, Titusville, USA,
5
Janssen Research &
Development, Oncology, Raritan, USA,
6
Janssen Research & Development,
Oncology, Raritan, USA,
7
Janssen Research & Development, Oncology,
Raritan, USA,
8
Weill Cornell Medicine, New York‐Presbyterian Hospital,
Hematology/Oncology, New York, USA
Introduction: Rituximab maintenance (MR) after first line (1L) R‐
CHOP improved overall survival (OS) in mantle cell lymphoma
(MCL) in clinical trials. How MR is used in routine clinical practice and
the benefits of MR after 1L BR are less defined. We evaluated the
real‐world patterns and outcomes of MR after 1L BR/R‐CHOP in a
large US MCL cohort.
Methods: This retrospective study included adult patients (pts) with
MCL diagnosed Jan 2011‐Nov 2020 in the nationwide Flatiron Health
EHR‐derived deidentified database. Pt characteristics, treatment (tx)
patterns, real‐world time to next tx (rwTTNT; 1L to subsequent tx or
death), and real‐world OS (rwOS) were evaluated for pts treated with
1L BR/R‐CHOP ± MR (entire cohort). Given the potential for MR se-
lection biases, analyses were performed in pts who were alive and did
not initiate subsequent tx within 8 months (mos) of starting 1L BR or 6
mos of R‐CHOP (MR‐eligible cohort). Multivariate analyses (MVA)
were performed for rwTTNT/OS on the effects of MR adjusting for age,
ECOG PS, lactate dehydrogenase level, white blood cell count, and
blastoid/pleomorphic and bulky disease status.
Results: Among 2946 pts with documented 1L MCL tx, 86.3% were
from a community oncology setting. In the entire cohort, 854 pts
received BR alone (median duration of tx [mDOT]: 4.1 mos), 368 BR
+ MR (mDOT: 25.7 mos), 365 R‐CHOP alone (mDOT: 3.5 mos), and
147 R‐CHOP + MR (mDOT: 26.9 mos). Median pt age for starting 1L
BR ± MR (72.8 years [yrs]) was older than R‐CHOP ± MR (66.4 yrs).
The 36‐mo rwTTNT rate was highest with BR + MR (72%), followed
by R‐CHOP + MR (68%). Median rwTTNT was reached at 17.0 and
7.8 mos for BR and R‐CHOP alone, respectively.
In the MR‐eligible cohort, 590 pts received BR alone (mDOT: 4.67
mos), 365 received BR + MR (mDOT: 25.8 mos), 207 received R‐CHOP
alone (mDOT: 4.0 mos), and 145 received R‐CHOP + MR (mDOT: 26.9
mos). Disease characteristics of intermediate/high MCL International
Prognostic Index or blastoid/pleomorphic biology were similar be-
tween BR/R‐CHOP with and without MR (Table). MVA showed that
MR was independently associated with longer rwTTNT (hazard ratio
[HR] 0.45; 95% confidence interval [CI], 0.38‐0.53; p < 0.001) and rwOS
(HR 0.56; 95% CI, 0.45‐0.7; p < 0.001). With estimated median follow‐
up of 38.9 mos (range 0.03‐117.1) for BR ± MR and 64.3 mos (range
0.03‐115.0) for R‐CHOP ± MR, the 36‐mo rwTTNT rate was 73% for
BR + MR and 69% for R‐CHOP + MR. Estimated median rwTTNT was
reached at 36 and 21.5 mos for BR and R‐CHOP alone, respectively.
The 36‐mo rwOS rate was 84% for BR + MR, 76% for BR alone, 89% for
R‐CHOP + MR, and 76% for R‐CHOP alone.
Conclusions: This is the largest real‐world MCL cohort treated with
1L BR or R‐CHOP, followed by MR. MR was associated with
improved rwTTNT and rwOS. The best rwTTNT rate was seen with
1L BR + MR. The phase 3 SHINE study (NCT01776840) is evaluating
the potential benefit of adding ibrutinib to BR + MR in pts with
previously untreated MCL.
EA – previously submitted to EHA 2021.
The research was funded by: Janssen Research & Development
TABLE: Baseline characteristics and clinical outcomes in the MR‐eligible cohort
SUPPLEMENT ABSTRACTS
-
219
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Combination
Therapies
Conflicts of interests pertinent to the abstract
M. Wang
Consultant or advisory role: AstraZeneca, Janssen Research and
Development, Celgene, MORE Health, Juno Therapeutics, Bioinvent,
Pharmacyclics/Janssen, Pulse Biosciences, AxImmune, Kite Pharma,
Noble Insights, Guidepoint Global, Loxo
Stock ownership: MORE Health
Honoraria: Janssen Research and Development, DAVA Oncology,
OM Pharmaceutical Industries, PeerView, Oncology business review,
OncLive, Pharmacyclics, AstraZeneca and Targeted Oncology
Research funding: AstraZeneca, Janssen Research and Development,
Pharmacyclics, Kite Pharma, Juno Therapeutics, BeiGene, Novartis,
Acerta Pharma, Oncternal Therapeutics, Amgen, BioInvent, Loxo,
VelosBio, Celgene and Versastem
Educational grants: Janssen Research and Development, AstraZe-
neca, Celgene, DAVA Oncology and OM Pharmaceutical Industries
G. Salles
Consultant or advisory role: Roche/Genentech, Gilead Sciences,
Janssen, Celgene, Novartis, MorphoSys, Epizyme, Alimera Science,
Genmab, Debiopharm group, VelosBio, Genmab, Bristol‐Myers
Squibb, BeiGene, Incyte and Miltenyi Biotec
Honoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences,
Novartis, Abbvie, and MorphoSys
A. Kumar
Consultant or advisory role: Kite (a Gilead company), Summit Advisory
Committee and Steering Committee for MCL Registry for AstraZeneca
Research funding: Abbvie, Adaptive Biotechnologies, Celgene, Phar-
macyclics, Seattle Genetics, AstraZeneca and AstraZeneca advisory
board
K. Qi
Employment or leadership position: Janssen
K. Daly
Employment or leadership position: Janssen
L. Parisi
Employment or leadership position: Janssen
A. Zhu
Employment or leadership position: Janssen
P. Martin
Consultant or advisory role: Celgene, Janssen, Bayer, Kite Pharma,
BeiGene, I‐Mab, MorphoSys, TeneoBio, Karyopharm Therapeutics,
Kite/Gilead, Verastem, Cellectar and Regeneron
Research funding: Karyopharm Therapeutics
Educational grants: Janssen
150 | RITUXIMAB IN COMBINATION WITH BENDAMUSTINE
OR HIGH‐DOSE CYTARABINE‐BASED INDUCTION THERAPY IN
TRANSPLANT‐ELIGIBLE PATIENTS WITH MANTLE CELL
LYMPHOMA
D. Villa
1
, E. Hoster
2
, O. Hermine
3
, W. Klapper
4
, M. Szymczyk
5
, A.
Bosly
6
, M. Unterhalt
7
, C. L. Freeman
1
, D. W. Scott
1
, A. S. Gerrie
1
, K. J.
Savage
1
, L. H. Sehn
1
, M. Dreyling
8
1
BC Cancer, Centre for Lymphoid Cancer, Vancouver, Canada,
2
Ludwig‐
Maximilians‐Universität München, Institute for Medical Information
Processing, Biometry, and Epidemiology , Munich, Germany,
3
University of
Paris Descartes, Hôpital Necker, Assistance Publique Hôpitaux de Paris,
Paris, France,
4
Universitätsklinikum Schleswig‐Holstein, Institut für
Pathologie, Sektion Hämatopathologie und Lymphknotenregister, Kiel,
Germany,
5
Maria Sklodowska‐Curie National Research Institute of
Oncology, Department of Lymphoid Malignancies, Warsaw, Poland,
6
CHU
UCL Mont‐Godinne‐Dinant, Faculty of Medicine and Dentistry, Yvoir,
Belgium,
7
University of Ulm, Department of Internal Medicine, Ulm,
Germany,
8
Ludwig‐Maximilians‐Universität München, Medizinische Klinik
III, Munich, Germany
TABLE 1
220
-
SUPPLEMENT ABSTRACTS
Introduction: The European Mantle Cell Lymphoma (MCL) Younger
study showed alternating R‐CHOP/R‐DHAP before autologous stem
cell transplant (ASCT) is associated with longer time to treatment
failure compared to R‐CHOP in young, fit patients. Rituximab in
combination with bendamustine (R‐B) achieves higher response rates
and progression‐free survival (PFS) compared to R‐CHOP in
transplant‐ineligible patients. The objective of this study was to
explore differences in outcomes between first‐line R‐B and R‐CHOP/
R‐DHAP in transplant‐eligible patients with MCL.
Methods: A cohort of 97 patients aged 18‐65 years with stage II‐IV
MCL, performance status 0‐2, and consecutively treated with R‐B
was identified using the BC Cancer Centre for Lymphoid Cancer
clinical and pathology databases. Baseline characteristics, response
rates, and outcomes were compared to the cohort of 232 patients
randomized to the R‐CHOP/R‐DHAP arm of the MCL Younger trial.
The primary aim was to estimate the hazard ratio (HR) of the PFS
comparison between both groups, adjusted for MIPI score as a
continuous variable, Ki67 index, and blastoid morphology. Additional
multivariate models evaluated the adjusted PFS HR for individual
variables and combinations. Secondary endpoints included response
rates, event free survival (EFS), overall survival (OS) and time to 2
nd
line therapy.
Results: Table 1 shows baseline characteristics. The overall response
rate (ORR) to R‐B was 89% (77% complete response [CR]); 77%
patients proceeded to ASCT, and 78% received maintenance ritux-
imab (MR). The ORR to R‐CHOP/R‐DHAP was 94% (54% CR); 78%
proceeded to ASCT, and 2% received MR.
After a median follow up of 4.3 years (range 0.2‐7.6) in the R‐B
group and 7.1 years (range 0.1‐14.8) in the R‐CHOP/R‐DHAP group,
there were no differences in PFS between both groups in unadjusted
analyses (5‐year rate 76% vs. 68%, respectively, HR 0.87 [95% CI
0.53‐1.41], p = 0.56), Figure 1. The HR for the comparison of R‐B vs.
R‐CHOP/R‐DHAP adjusted for MIPI, Ki67 ≥30%, and blastoid
morphology was 0.79 (95% CI 0.45‐1.37), p = 0.40. The HR were
below 1 but far from statistical significance in models adjusting the
treatment comparison for MIPI, individual MIPI variables, Ki67, or
blastoid morphology individually or in combinations.
There were no clear differences in EFS in unadjusted (5‐year rate
70% vs. 65%, HR 0.88 [95% CI 0.56‐1.37], p = 0.570) or adjusted
analyses (HR 0.75 [95% CI 0.45‐1.25], p = 0.27). There were no clear
differences in OS in unadjusted (5‐year rate 79% vs. 77%, HR 0.81
(95% CI 0.46‐1.40], p = 0.44, Figure 2) or adjusted analyses (HR 0.65,
95% CI 0.24‐1.24). Time to second‐line therapy was also similar (5‐
year rate 25% vs. 28%, p = 0.97).
Conclusion: In this retrospective comparison of two independent
cohorts of younger patients with MCL, there were no marked dif-
ferences in outcomes between first‐line R‐B with ASCT and MR
compared to R‐CHOP/R‐DHAP with ASCT.
Keywords: Indolent non‐Hodgkin lymphoma, Chemotherapy, Stem
Cell Transplant
No conflicts of interest pertinent to the abstract.
151 | PREDICTION OF RELAPSE BY STANDARDIZED IG‐BASED
ALLEL‐SPECIFIC QPCR, DDPCR AND AMPLICON NGS FOR MRD
MONITORING IN MANTLE CELL LYMPHOMA: A COMPARATIVE
ANALYSIS BY THE EU‐MCL NETWORK
C. Pott
1
, E. Macintyre
2
, M.‐H. Delfau
3
, A. Weiß
4
, A. Schilhabel
1
, A.
Soehlbrand
1
, B. Kehden
1
, N. Darzentas
1
, M. Kotrova
1
, F. Schoen
1
, V.
Ribrag
5
, M. Brueggemann
1
, P. Villarese
6
, M. Dreyling
7
, O. Hermine
8
,
H. Kluin‐Nelemans
9
, L. Jiang
10
, E. Hoster
10
1
University Hospital Schleswig‐Holstein, Medical Department II, Kiel,
Germany,
2
Université de Paris (Descartes), Hématologie Biologique and
INSERM UMR1151, Paris, France,
3
Mondor Biomedical Research
FIGURE 1
FIGURE 2
SUPPLEMENT ABSTRACTS
-
221
Institute, Department of hematology and immune biology, Creteil, France,
4
University of Schleswig‐Holstein, Center for Structural and Cell Biology in
Medicine, Luebeck, Germany,
5
Institut Gustave Roussy, Department of
Hematology, Villejuif, France,
6
Hôpital Necker Enfants Malades, DMU
Biologie medical, Paris, France,
7
Ludwig‐Maximilian University Munich,
Medical Department III, Munich, Germany,
8
Université Sorbonne Paris
Cité, Department of Clinical Hematology, Paris, France,
9
University
Medical Center Groningen, Department of Hematology, Groningen,
Netherlands,
10
Ludwig‐Maximilians‐University Munich, Institut für Med-
izinische Informationsverarbeitung Biometrie und Epidemiologie, Munich,
Germany
Introduction: MRD monitoring is of high prognostic value in patients
with MCL. Allele‐specific real‐time quantitative PCR (qPCR) of clonal
immunoglobulin gene (IG) rearrangements is the gold standard for
MRD quantification but is limited by a quantitative level of 10E‐04
and less specific results below the quantitative range (BQR). Digital
droplet PCR (ddPCR) allows direct MRD quantification, while next
generation sequencing (NGS) can overcome the limitation of PCR‐
based approaches with a potential higher sensitivity. We compared
qPCR, ddPCR and IG‐NGS for MRD quantification and prognostica-
tion in MCL.
Methods: 163 diagnostic and 356 follow‐up samples from 163 pa-
tients of the EU‐MCL younger and elderly trials were selected based
on the presence of BQR MRD by qPCR. 3 � 500 ng DNA was ana-
lysed in order to achieve a sensitivity of 10E‐05, with multiplex 1‐ or
2‐step EuroClonality IGH‐VJ‐FR1/2 PCR and an Illumina MiSeq.
Reference standard DNA was spiked into each sample to allow NGS‐
MRD quantification by normalization of NGS reads to cell copy
numbers. Dominant IG clonotypes were identified in diagnostic
samples at abundance level ≤5% of total IGH reads. Data were
analysed by ARResT/Interrogate including built‐in spike‐based
quantification. To compare different methods for prediction of clin-
ical relapse, MRD results in blood of patients in remission for at least
12 months after ASCT or induction were correlated with time to
progression.
Results: Dominant IG clonotypes were detected in all diagnostic
samples, thus confirming Sanger sequencing. MRD by qPCR was
positive quantifiable in 194/519 samples and BQR in 173, 152
samples were negative. NGS confirmed 120/173 qPCR BQR samples
(69%) as true positive, while ddPCR confirmed 102/173 (59%). Of
356 FU samples, 110 were concordantly negative and 117 were
positive by all three methods. False negativity by one method,
determined as MRD positivity by the two other methods, were 4% by
RQ‐PCR, 17% by ddPCR and 7.7% by NGS, false positivity was 11%,
6% and 5% respectively. In blood samples from 170 patients in
remission at least 12 months after ASCT or induction, accuracy of
both methods in comparison to qPCR as reference standard was
higher for NGS with a better sensitivity and specificity compared to
ddPCR. The closest agreement of MRD results was among NGS and
qPCR. Prediction of relapse correlated well among the 3 methods,
demonstrating a strong effect of MRD positive quantifiable with a HR
of 4.4 (2.5 – 7.9) in qPCR, 3.8 (2.3 – 6.1) in ddPCR and 4.0 (2.6 – 6.3)
by NGS compared with MRD negatives.
Conclusion: EuroClonality NGS demonstrates broad applicability in
MCL and enables a more specific readout compared to PCR based
FIGURE 1 Time to progression to MRD status by qPCR, ddPCR and NGS
222
-
SUPPLEMENT ABSTRACTS
methods. NGS and ddPCR virtually abolish the non‐quantifiable low‐
level positivity of qPCR. All three methods identify comparable
prognostic subgroups with the best prognostication by NGS and
confirm the high prognostic impact of MRD detection.
Keywords: Minimal residual disease
No conflicts of interest pertinent to the abstract.
152 | HIGH‐RISK MANTLE CELL LYMPHOMA IN THE LYMA
TRIAL: A LYSA STUDY
M. Cheminant
1
, B. Burroni
2
, Y. Le Bris
3
, L. Chartier
4
, L. Oberic
5
, V.
Ribrag
6
, M.‐H. Delfau
7
, C. Thieblemont
8
, R. Gressin
9
, D. Canioni
1
, M.
Peyre
1
, C. Laurent
10
, T. Steimle
1
, S. Kaltenbach
1
, V. Asnafi
1
, E.
Macintyre
1
, M. Callanan
11
, S. Le Gouill
12
, O. Hermine
1
1
Necker‐Enfants Malades University Hospital, Adult Hematology,
75015, France,
2
Cochin University Hospital, Pathology, Paris, France,
3
Nantes University Hospital, Hematolobiology, Nantes, France,
4
LYSARC, Statistics, Lyon, France,
5
Toulouse‐Oncopole University
hospital, Hematology, Toulouse, France,
6
Gustave‐Roussy, Hematology,
Villejuif, France,
7
Mondor University Hospital, Hematolobiology, Créteil,
France,
8
Saint Louis University Hospital, Hematology, Paris, France,
9
Grenoble University Hospital, Hematology, Grenoble, France,
10
LYSARC,
Bio‐informatics, Paris, France,
11
Dijon University Hospital, Hematobiol-
ogy, Dijon, France,
12
Nantes University Hospital, Hematology, Nantes,
France
Background: Around 5‐10% of mantle cell lymphoma (MCL) patients
are primary refractory to chemotherapy. They have an extremely
dismal prognosis, similar to responsive patients that relapsed within
12 months. Despite better understanding of risk factors and evolving
classifications, these scores could not predict all high‐risk patients
and were not designed to guide treatment strategy in newly diag-
nosed MCL.
Aim: We conducted an ancillary study in a prospective phase III trial
randomizing observation versus Rituximab maintenance after R‐
DHAP followed by ASCT (LyMa Trial; Le Gouill et al, NEJM 2017).
Herein, we report our study of high‐risk MCL patients.
Methods: High‐risk MCL patients were defined as being primary
chemo‐refractory or having relapsed within 12 months following
randomization (Visco BJH 2018).
Results: Among the 299 MCL patients included in the LyMa trial, 31
high‐risk MCL patients were identified (10.4%). Their characteristics
at baseline were similar to control patients (n = 268), regarding age,
performance status, Ann Arbor staging, presence of B symptoms.
High‐risk patients had more often elevated LDH (65% vs. 38%, p =
0.006), high‐risk MIPI score (45% vs. 16%, p < 0.001), Ki‐67 > 30%
(71% vs. 31%, p < 0.001) and blastoid/pleomorphic histology (32% vs.
9%, p < 0.001). In multivariate analysis, high‐risk MIPI score and Ki‐
67 > 30% were associated with high‐risk MCL. There was no sig-
nificant difference in terms of TP53 expression between high‐risk
and control MCL. Many high‐risk MCL patients have been classified
as low‐risk at diagnosis, with 36% of them having a low‐risk MIPI
score and 29% having a Ki‐67 ≤ 30%. High‐risk patients had more
often positive MRD pre‐ASCT in blood (47.1% vs. 20.6%, p = 0.029)
and had more positive PET pre‐ASCT (48% vs. 25.6%, p = 0.032).
Median OS was 17 months in high‐risk MCL patients, compared to 68
months in late progressors (95% CI, 12 to 26 months vs. 47 to not
reached respectively, p < 0.001). At relapse, 11/31 (36%) had a CNS
involvement. Salvage therapies consisted of chemotherapy in 26
patients (CHOP, MTX‐AraC, bendamustine, VR‐CAP), rituximab in
26, temsirolimus in five, lenalidomide and combination of ibrutinib
and lenalidomide in two other patients, as second line therapy.
Ibrutinib was also used in two other patients as third line. Overall
response rate was 37%, with 27% of complete response. Seven pa-
tients received allogeneic stem cell transplantation, of whom four
died, from toxicity in two and from lymphoma in two. Median PFS
and OS were 19.2 months and not reached for responding patients
compared to 3.2 and 8.2 months for stable/progressive disease
respectively.
Conclusion: Known risk factors do not perfectly identify high‐risk
MCL patients at baseline. High‐risk patients with early disease pro-
gression had an extremely dismal prognosis and should receive
innovative strategies combined with systematic CNS prophylaxis as
salvage therapy.
EA – previously submitted to EHA 2021.
Keywords: Diagnostic and Prognostic Biomarkers, Indolent non‐
Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
153 | REAL‐WORLD TREATMENT PATTERNS AND OUTCOMES
OF 3455 PREVIOUSLY UNTREATED MANTLE CELL LYMPHOMA
PATIENTS IN US ROUTINE CLINICAL PRACTICE
A. Kumar
1
, P. Martin
2
, M. Wang
3
, K. Qi
4
, K. Daly
5
, L. Parisi
6
, A. Zhu
7
,
G. Salles
8
1
Memorial Sloan Kettering Cancer Center, Lymphoma Service at the
Department of Medicine, New York, New York, USA,
2
Weill Cornell
Medicine, New York‐Presbyterian Hospital, Hematology/Oncology, New
York, USA,
3
The University of Texas MD Anderson Cancer Center,
Department of Lymphoma/Myeloma, Houston, USA,
4
Janssen
Research & Development, IHI RWE, Titusville, USA,
5
Janssen
Research & Development, Oncology, Raritan, USA,
6
Janssen Research &
Development, Oncology, Raritan, USA,
7
Janssen Research & Develop-
ment, Oncology, Raritan, USA,
8
Memorial Sloan Kettering Cancer
Center, Lymphoma Service at the Department of Medicine, New York,
USA
Introduction: Mantle cell lymphoma (MCL) is a non‐Hodgkin's lym-
phoma with heterogeneous biology and outcomes. We characterized
real‐world (RW) treatment (tx) patterns and outcomes of patients
(pts) with MCL to identify factors associated with outcomes in
the US.
SUPPLEMENT ABSTRACTS
-
223
Methods: This retrospective study included adult pts with MCL
diagnosed between January 2011 and November 2020 in the
nationwide Flatiron Health Electronic Health Records‐derived dei-
dentified database (“MCL‐eligible”). Pt characteristics, tx patterns,
RW time‐to‐next tx (rwTTNT, defined as start of first‐line [1L] tx to
subsequent tx or death), and RW overall survival (rwOS) were
evaluated.
Results: 3455 pts were included, 85.3% from a community oncology
setting. In 2946 (85.2%) pts with documented 1L MCL tx, median age
was 69.5 years (range, 27.7‐85.3); 9.5% had blastoid/pleomorphic
MCL. 262 (39.6%) and 235 (35.6%) of 661 pts with available MCL
international prognostic index had intermediate and high risk,
respectively. 150/1253 pts (12.0%) with available Eastern Coopera-
tive Oncology Group performance status (ECOG PS) had an ECOG
PS ≥ 2. Chemoimmunotherapy was the most common 1L tx, including
bendamustine plus rituximab (BR) in 1223 (41.5%), rituximab plus
cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐
CHOP) in 512 (17.4%), and cytarabine (ara‐C)‐containing tx in 414
(14.1%). 667 pts received R maintenance (MR). In 1036 pts < 65
years, 243 pts received 1L stem cell transplant (SCT), mainly autol-
ogous. In 1L‐treated pts, with a median follow‐up of survivors of 45.3
months (range, 0.03‐117.2), median rwTTNT was 24 months;
36‐month rwOS was 67%. The Table shows tx received and out-
comes by age and SCT status. Multivariate analyses showed age ≥65
years, ECOG PS ≥2, lactate dehydrogenase/upper limit of normal ≥1,
white blood cell count ≥10 � 10
9
/L, bulky disease (≥5 cm), and
blastoid/pleomorphic morphology were associated with shorter
rwTTNT and rwOS; MR was independently associated with longer
rwTTNT and rwOS. In pts < 65 years who were alive and did not
initiate subsequent tx within 6 months of 1L tx (“SCT‐eligible”), 36‐
month rwTTNT and rwOS were similar between pts treated with
versus without SCT: 65% versus 59% and 86% versus 85%,
respectively.
Conclusions: In this large RW cohort of primarily community‐based
US practices, median 1L rwTTNT for pts with MCL was ∼2 years.
BR was the most commonly used 1L tx. SCT was uncommon even in
pts < 65 years, suggesting RW considerations may influence SCT
eligibility and availability. Additionally, SCT was not clearly
associated with rwOS. As with other reports, older age and high‐risk
disease features were predictive of worse outcome in RW, while MR
appeared to be associated with better outcomes. Outcomes across
the board appear worse than prospective trials, suggesting a need to
focus on developing tx that can be delivered effectively in the com-
munity setting.
EA – previously submitted to ASCO and EHA 2021.
The research was funded by: Janssen Research & Development
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
A. Kumar
Consultant or advisory role: Kite (a Gilead company), Summit Advisory
Committee and Steering Committee for MCL Registry for AstraZeneca
Research funding: Abbvie, Adaptive Biotechnologies, Celgene, Phar-
macyclics, Seattle Genetics, AstraZeneca and AstraZeneca advisory
board
P. Martin
Consultant or advisory role: Celgene, Janssen, Bayer, Kite Pharma,
BeiGene, I‐Mab, MorphoSys, TeneoBio, Karyopharm Therapeutics,
Kite/Gilead, Verastem, Cellectar and Regeneron
Research funding: Karyopharm Therapeutics
Educational grants: Janssen
M. Wang
Consultant or advisory role: AstraZeneca, Janssen Research and
Development, Celgene, MORE Health, Juno Therapeutics, Bioinvent,
Pharmacyclics/Janssen, Pulse Biosciences, AxImmune, Kite Pharma,
Noble Insights, Guidepoint Global, Loxo
Stock ownership: MORE Health
Honoraria: Janssen Research and Development, DAVA Oncology,
OM Pharmaceutical Industries, PeerView, Oncology business review,
OncLive, Pharmacyclics, AstraZeneca and Targeted Oncology
Research funding: AstraZeneca, Janssen Research and Development,
Pharmacyclics, Kite Pharma, Juno Therapeutics, BeiGene, Novartis,
Acerta Pharma, Oncternal Therapeutics, Amgen, BioInvent, Loxo,
VelosBio, Celgene and Versastem
TABLE: Tx and outcomes in 1L MCL
224
-
SUPPLEMENT ABSTRACTS
Educational grants: Janssen Research and Development, AstraZe-
neca, Celgene, DAVA Oncology and OM Pharmaceutical Industries
K. Qi
Employment or leadership position: Janssen
K. Daly
Employment or leadership position: Janssen
L. Parisi
Employment or leadership position: Janssen
A. Zhu
Employment or leadership position: Janssen
G. Salles
Consultant or advisory role: Roche/Genentech, Gilead Sciences,
Janssen, Celgene, Novartis, MorphoSys, Epizyme, Alimera Science,
Genmab, Debiopharm group, VelosBio, Genmab, Bristol‐Myers
Squibb, BeiGene, Incyte and Miltenyi Biotec
Honoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences,
Novartis, Abbvie, and MorphoSys
EXTRANODAL LYMPHOMA
154 | PROGNOSTIC FACTORS, MANAGEMENT AND OUTCOME
OF AN INTERNATIONAL SERIES OF 41 PATIENTS WITH PRIMARY
MEDIASTINAL LARGE B‐CELL LYMPHOMA (PMLBCL) AND
CENTRAL NERVOUS SYSTEM (CNS) INVOLVEMENT
A. J. M. Ferreri
1
, V. Tarantino
2
, G. Cabras
3
, F. Ferrara
4
, P. L. Zinzani
5
,
L. Arcaini
6
, A. Castellino
7
, A. Tucci
8
, F. Cocito
9
, A. Davies
10
,
M. M. B Salvador Chalup
11
, K. Cwynarski
12
, F. L. Nogueira
13
,
L. Petrucci
14
, C. Muzi
15
, D. Onofrillo
16
, A. Ferrario
17
,
P. Ramakrishnan
18
, P. R. Scalzulli
19
, M. Tani
20
, M. C. Tisi
21
,
S. G. Papageorgiou
22
, T. Calimeri
1
, P. Angelillo
1
, M. Foppoli
1
,
M. Dimou
23
, M. Ponzoni
24
, E. Iannitto
25
, T. P. Vassilakopoulos
26
1
IRCCS San Raffaele Scientific Institute, Lymphoma Unit, Dept. of Onco‐
Hematology, Milano, Italy,
2
University of Modena and Reggio Emilia,
PhD Program in Clinical and Experimental Medicine, Modena, Italy,
3
Ospedale Oncologico, Struttura Complessa di Ematologia e CTMO,
Cagliari, Italy,
4
AORN Cardarelli Hospital, Division of Hematology and
Stem Cell Transplantation Program, Naples, Italy,
5
IRCCS Azienda
Ospedaliero‐Universitaria di Bologna, Istituto di Ematologia “Seràgnoli,
Bologna, Italy,
6
Fondazione IRCCS Policlinico San Matteo & Department
of Molecular Medicine, University of Pavia, Division of Hematology, Pavia,
Italy,
7
AO di Cuneo, Division of Hematology, Cuneo, Italy,
8
ASST Spe-
dali Civili, Hematology Department, Brescia, Italy,
9
ASST‐Monza, UC
di Ematologia, Monza, Italy,
10
CRUK Centre, University of Southampton,
Faculty of Medicine, Southampton Experimental Cancer Medicines
Centre, Southampton, UK,
11
Hematológica, Oncoclínicas, Hematological
Malignancies and Stem Cell Transplantation, Belo Horizonte, Brazil,
12
University College London Hospitals, Department of Haematology,
London, UK,
13
Gurpo Oncoclínicas, Clínica Hematologica, Belo Horizonte,
Minas Gerais, Brazil,
14
University Sapienza, Hematology Department of
Translation and Precision Medicine, Rome, Italy,
15
ASST Grande Ospe-
dale Metropolitano Niguarda, Division of Haematology, Milan, Italy,
16
Spirito Santo Hospital, Pediatric Hematology and Oncology Unit,
Department of Hematology, Pescara, Italy,
17
ASST Sette Laghi, Hema-
tology, Varese, Italy,
18
Harold C. Simmons Comprehensive Cancer Cen-
ter, UT Southwestern Medical Center, Division of Hematologic
Malignancies and Cellular Therapy, Dallas, Texas, USA,
19
Fondazione
IRCCS “Casa Sollievo della Sofferenza”, Division of Hematology, San
Giovanni Rotondo, Italy,
20
Santa Maria delle Croci Hospital, Hematolo-
gy Unit, Ravenna, Italy,
21
San Bortolo Hospital, Cell Therapy and Hema-
tology, Vicenza, Italy,
22
University General Hospital “Attikon”, National
and Kapodistrian University of Athens, Second Department of Internal
Medicine, Propaedeutic, Hematology Unit, Athens, Greece,
23
Gen-
eral Hospital, National and Kapodistrian University of Athens, First
Department of Internal Medicine, Propaedeutic, Haematology Clinical
Trial Unit, Athens, Greece,
24
Università Vita‐salute San Raffaele, Milano,
Italy, Pathology Unit, Milan, Italy,
25
Casa di Cura “La Maddalena”,
Hematology and BMT, Department of Oncology, Palermo, Italy,
26
Laikon
General Hospital, National and Kapodistrian University of Athens,
Department of Haematology and Bone Marrow Transplantation, Athens,
Greece
Introduction: CNS dissemination is an uncommon event in PMLBCL.
International cooperation is an important tool to improve our
knowledge on this poorly‐investigated condition.
Methods: Data from PMLBCL pts with CNS disease at presentation
or relapse treated at 24 Centers from 6 countries were analyzed.
Results: 41 pts (median age 32, range 14‐52; 22 males) were
considered. At initial lymphoma diagnosis, 20 (49%) had advanced
stage, 21 (51%) B symptoms, 39 (95%) bulky disease, 37 (90%) raised
LDH, 18 (44%) had extranodal disease (16 in abdomen), 26 (63%) had
an aaIPI ≥2. First‐line treatment was CHOP14/21 in 20 pts, daE-
POCH in 6, M/VACOP‐B in 15, combined with rituximab in 39 (95%),
and followed by mediastinal irradiation in 14. CNS prophylaxis was
administered in 6 pts.
CNS involvement was recorded at initial diagnosis in one (2%) pt,
at first relapse in 34 (83%), at 3
rd
‐4
th
relapse in 6 (15%), with a
median time to CNS relapse of 7 (0‐24) months. CNS was the only
site of recurrence in 24 (59%) pts, all at first relapse. Brain or cere-
bellum were involved in 38 (93%) pts, associated with meningeal
infiltration in 6 of them, spinal cord in 1; meninges were the exclusive
site of disease in 2 (5%) pts.
Treatment was followed by complete remission in 13 pts (32%;
95%CI = 18‐46), all of them were treated at presentation or first
relapse, and, with a single exception, received high‐dose‐
methotrexate (HD‐MTX)‐based therapy plus ASCT ± WBRT (Ta-
ble). Twenty‐four treated pts experienced further tumor failure,
SUPPLEMENT ABSTRACTS
-
225
invariably in the CNS, with concomitant systemic disease in 8; 10 pts
with progressive disease limited to the CNS received WBRT, com-
bined with ASCT and/or other drugs, 8 achieving a CR lasting 16‐84
months (Table). Pts with CNS involvement at 3
rd
‐4
th
relapse also had
systemic, uncontrolled disease, and did not benefit from treatment.
At a median follow‐up of 61 (10‐173) months, 9 pts remain
relapse‐free, with a 5‐yr PFS after CNS relapse of 21±6%, and 17 pts
are alive, with a 5‐yr survival after CNS relapse of 42±8%. Systemic
disease and meningeal infiltration were not associated with outcome.
The 5‐yr survival after CNS relapse of the 26 pts treated with HD‐
MTX‐based combinations was 52±10%.
Conclusions: Advanced stage, abdominal extranodal disease and high
LDH levels are often recorded in PMLBCL pts with CNS recurrence.
Unlike other aggressive lymphomas, CNS involvement at presentation
and meningeal infiltration are rare in PMLBCL. Prognosis is poor, but
HD‐MTX‐based therapy and consolidative ASCT are associated with
encouraging results. WBRT contributes to the achievement of long‐
lasting remission even in pts with chemorefractory disease.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Lymphoid
Cancers ‐ Other
No conflicts of interest pertinent to the abstract.
155 | LIQUID‐BIOPSY BASED GENOTYPING OF PRIMARY
CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL)
J.‐M. Heger
1
, P. Gödel
1
, H. Balke‐Want
1
, J. Altmüller
2
, J. Mattlener
1
,
H. Dörr
1
, J. Weiss
1
, N. Sieg
1
, N. Kutsch
1
, H. C. Reinhardt
3
, P. Borch-
mann
1
, B. von Tresckow
3
, S. Borchmann
1
1
Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO
ABCD), University of Cologne, Faculty of Medicine and University Hospital
of Cologne, Department I of Internal Medicine, Cologne, Germany,
2
University of Cologne, West German Genome Center, Cologne, Germany,
3
West German Cancer Center, University Hospital Essen, University of
Duisburg‐Essen, Department of Hematology and Stem Cell Trans-
plantation, Essen, Germany
Introduction: In Primary Central Nervous System Lymphoma
(PCNSL) tissue samples are mainly obtained through stereotactic or
open surgical biopsies, bearing significant risks. Furthermore, the
genomic landscape of PCNSL is less well described than in diffuse
large B‐cell lymphoma (DLBCL). Consequently, sequencing of circu-
lating tumor DNA (ctDNA) could be a helpful tool to minimally
invasively genotype PCNSL at diagnosis and even more importantly,
at relapse, when repeat biopsies are not routinely performed due to
associated risks. Response assessment is currently carried out by
magnetic resonance imaging (MRI) but lacks accuracy in dis-
tinguishing remaining scar tissue from active lymphoma. Thus, a high
unmet medical need for improved prognostic assessment including
genotyping and highly sensitive response monitoring aided by ctDNA
sequencing exists.
Methods: Cell‐free DNA (cfDNA) was extracted from plasma samples
of 17 patients suffering from previously untreated PCNSL between
8/2018 and 4/2020. CfDNA sequencing targeted a newly designed
panel of ∼350 genes. Sequencing and bioinformatic analysis was
performed as previously published (Sobesky et al., bioRxiv 2021).
Results: We successfully extracted sufficient cfDNA in 17/17 (100%)
of patients from 4 ml plasma. The median amount of cfDNA was 16,7
ng/ml plasma (range 1,4‐119,9 ng/ml). Overall, 120 different genes
TABLE
226
-
SUPPLEMENT ABSTRACTS
displayed somatic variants (SNVs or InDels). Somatic variants were
detectable in all patients with a median of 10 mutations per patient
(range 1‐43). Overall, we identified 29 significantly mutated genes by
MutSig2CV analysis (Figure 1). Among the most recurrently mutated
genes were KMT2D (7 patients), NFKBIA (4 patients) and EP300 (4
patients). The mutated allele frequency was generally low (median
0.95%; range 0.14%‐16.00%). KMT2D and KMT2B mutations had high
allele frequencies, suggesting they constitute events early in PCNSL
oncogenesis. Surviving patients had significantly lower ctDNA burden
measured by average mutated allele frequency than patients who died
(1,61% vs. 4,13%; p = 0,011). At the meeting, a full analysis of our
cohort including copy number variations and further genotype‐
phenotype links will be presented.
Conclusions: Our results show that detection of ctDNA in peripheral
blood of patients suffering from PCNSL is feasible. Furthermore, we
were able to detect several recurrent genetic aberrations that were
previously shown to be present in DLBCL as well as PCNSL in tissue
genotyping. Despite the fact that the mutated allele frequency was
rather low compared to previous reports from DLBCL, our pipeline
allowed us to detect genetic aberrations in 100% of cases in our
series. Liquid biopsy‐based genotyping of PCNSL might offer
tremendous advantages for diagnostic approaches, discovery of
potential therapeutic targets and assessment of response or early
detection of relapse.
The research was funded by: Else‐Kröner‐Fresenius‐Stiftung
Keywords: Liquid biopsy, Extranodal non‐Hodgkin lymphoma, Pa-
thology and Classification of Lymphomas
No conflicts of interest pertinent to the abstract.
156 | SARS‐COV‐2 INFECTION IN 50 PATIENTS WITH
PRIMARY CNS LYMPHOMA: PRESENTATION, EFFECTS ON
TUMOR TREATMENT AND OUTCOME IN A SERIES OF THE
INTERNATIONAL PCNSL COLLABORATIVE GROUP
A. J. M. Ferreri
1
, S. Steffanoni
1
, T. Calimeri
1
, A. Laurenge
2
, C. P. Fox
3
,
C. Soussain
4
, C. Grommes
5
, M. C. Sassone
1
, M. Touat
2
, J. Boot
6
,
N. Crosbie
7
, S. Chaganti
8
, J. Dietrich
9
, A. Alencar
10
, G. Itchaki
11
,
K. Hoang Xuan
12
, T. Batchelor
12
, K. Cwynarski
13
1
IRCCS San Raffaele, Lymphoma Unit, Hematology, Milan, Italy,
2
Hôpitaux Universitaires La Pitié Salpêtrière, Service de Neurologie 2‐
Mazarin, Paris, France,
3
University Hospitals NHS Trust, hematology,
Nottingham, UK 4 Hôpital René Huguenin‐Institut Curie, Saint‐Cloud,
FIGURE 1 Somatic variants (SNVs or InDels) limited to significant genes (p < 0.05) following MutSig2CV analysis
SUPPLEMENT ABSTRACTS
-
227
Hematology, Paris, France,
5
Memorial Sloan Kettering Cancer Center,
Department of Neurology, New York, USA,
6
Barking, Havering and Red-
bridge University Hospitals NHS Trust, Hematology, London, UK,
7
Derri-
ford Hospital, Hematology, Plymouth, UK,
8
Queen Elizabeth Hospital,
Haematology, Birmingham, UK,
9
Massachusetts General Hospital Cancer
Center, Neuro‐Oncology, Boston, USA,
10
University of Miami/Sylvester
Comprehensive Cancer Center, Department of Hematology and Oncology,
Miami, USA,
11
Davidoff Cancer Center, Rabin Medical Center, Hematol-
ogy, Petah‐Tikva, Israel,
12
Brigham and Women's Hospital, Neurology,
Boston, Massachusetts, USA,
13
University College London Hospital, Hae-
matology, London, UK
Introduction: COVID‐19 is associated with high mortality in can-
cer patients (pts); its course varies greatly among patient sub-
groups and tumor status. Herein, we report an international study
on pts with primary CNS lymphoma (PCNSL), an aggressive tumor
where dose intensity is crucial, and concurrent SARS‐CoV‐2
infection.
Methods: Data of presentation, management and outcome of pts
with PCNSL and SARS‐CoV‐2 infection were analyzed to define ef-
fects of infection on timing of anti‐lymphoma treatment and overall
outcome. Pts were grouped in 1st and 2nd pandemic waves using
July 31, 2020 as cut‐off for SARS‐CoV‐2 diagnosis.
Results: 50 pts from 12 centers of 5 countries were registered (Ta-
ble): 30 during 1st and 20 at 2nd wave. SARS‐CoV‐2 was diagnosed
before/during 1st‐line PCNSL treatment in 35 (70%) pts, with a
median time between PCNSL diagnosis and virus detection of 45
days (d) (range ‐27‐179). 26 of these pts (75%) developed pneumonia,
were hospitalized (median 22 d; 5‐192), 9 admitted to ICU (median
14 d; 1‐51); 13/26 (50%), cleared the virus (median time 31 d; 1‐69),
resumed anti‐lymphoma treatment (median treatment delay 27 d; 0‐
112) and were alive at the last visit. The 13 pts with pneumonia who
did not clear virus died of COVID‐19 or related infections within 25
d from symptoms onset. 8 of the 9 pts without pneumonia cleared
virus and resumed/initiated anti‐lymphoma treatment (median delay
16 d; 0‐93); none died of COVID‐19. Virus clearance and pneumonia
were significantly associated with resumption of anti‐lymphoma
treatment.
5 of 11 pts affected by SARS‐CoV‐2 during lymphoma follow‐up
developed pneumonia, required hospitalization (median 25 d; 5‐25).
All 11 pts cleared virus and are alive. Conversely, the 4 pts infected
during salvage anti‐lymphoma therapy, interrupted treatment, were
unable to clear virus and died of lymphoma or COVID‐19.
At a median follow‐up since virus detection of 214 d (0‐322), 30
(60%) pts are alive, 15 without evidence of lymphoma and 28 cleared
virus. SARS‐CoV‐2 serology was positive in 7/11 assessed survivors.
228
-
SUPPLEMENT ABSTRACTS
12 (24%) pts died of COVID‐19, 3 of other infections and 4 of lym-
phoma. The 6‐month OS was 63%; virus persistence was indepen-
dently associated with poor outcome. Mortality among pts in 1st line
treatment was significantly higher during the 2nd wave (4‐month OS:
75% vs 37%, p = 0.03), and associated with a lower viral eradication
rate (75% vs 40%; p = 0.03).
Conclusions: COVID‐19 was a strong outcome‐defining event,
especially in pts receiving anti‐PCNSL treatment and those diagnosed
during the 2nd wave. Multidisciplinary strategy facilitated eradica-
tion of the infection and completion of planned therapy, with
acceptable timing and short‐term OS rate, in half of pts with pneu-
monia. For pts in follow up, SARS‐CoV‐2 infection was not associated
with severe symptoms and did not affect OS. Poor results in pts
treated during the 2
nd
wave deserve particular attention.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Extranodal
non‐Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
157 | OLDER PATIENTS WITH PRIMARY CENTRAL NERVOUS
SYSTEM LYMPHOMA (PCNSL): REAL WORLD (RW) OUTCOMES
OF POST‐INDUCTION THERAPY IN THE MODERN ERA
K. A. David
1
, S. Sundaram
2
, S.‐H. Kim
3
, R. Vaca
4
, Y. Lin
5
, S. Singer
6
,
M.‐K. Malecek
7
, J. Carter
8
, A. Zayac
9
, M. S. Kim
10
, N. Reddy
11
,
D. Ney
12
, A. Habib
13
, C. Strouse
14
, J. Graber
15
, V. Bachanova
16
,
S. Salman
17
, J. A. Vendiola
17
, N. Hossain
17
, M. Tsang
18
, A. Major
19
,
D. B. Bond
20
, P. Agrawal
21
, A. Mier‐Hicks
2
, P. Torka
2
, P. Rajakumar
3
,
P. Venugopal
3
, S. Berg
17
, M. Glantz
22
, S. Goldlust
6
, P. Kumar
8
, T.
Ollila
9
, J. Cai
10
, S. Spurgeon
10
, A. Sieg
14
, J. Cleveland
18
, N. Epperla
20
,
R. Karmali
23
, S. Naik
4
, P. Martin
21
, S. M. Smith
19
, J. Rubenstein
18
,
B. Kahl
7
, A. M. Evens
8
1
Rutgers Cancer Institute of New Jersey, Division of Blood Disorders, New
Brunswick, New Jersey, USA,
2
Roswell Park Cancer Institute, Hematology/
Oncology, Buffalo, New York, USA,
3
Rush University Medical Center,
Hematology/Oncology, Chicago, Illinois, USA,
4
Penn State Cancer
Institute, Hematology/Oncology, Hershey, Pennsylvania, USA,
5
Rutgers
University, School of Public Health, New Brunswick, New Jersey, USA,
6
John Theurer Cancer Center, Brain and Spine Institute, Hackensack, New
Jersey, USA,
7
Washington University School of Medicine, Hematology/
Oncology, Saint Louis, Missouri, USA,
8
Rutgers Cancer Institute of New
Jersey, Division of Blood Disorders, New Brunswick, New Jersey, USA,
9
Brown University Alpert Medical School, Hematology/Oncology,
Providence, Rhode Island, USA,
10
Oregon Health and Sciences University,
Knight Cancer Institute, Portland, Oregon, USA,
11
Vanderbilt University
School of Medicine, Hematology/Oncology, Nashville, Tennessee, USA,
12
University of Colorado, Neurology, Denver, Colorado, USA,
13
University
of Minnesota, Hematology/Oncology, Minneapolis, Minnesota, USA,
14
University of Iowa School of Medicine, Hematology/Oncology, Iowa City,
Iowa, USA,
15
University of Washington School of Medicine, Neurology,
Seattle, Washington, USA,
16
University of Minnesota School of Medicine,
Hematology/Oncology, Minneapolis, Minnesota, USA,
17
Loyola University,
Stritch School of Medicine, Chicago, Illinois, USA,
18
University of
California School of Medicine, Hematology/Oncology, San Francisco,
California, USA,
19
University of Chicago School of Medicine, Hematology/
Oncology, Chicago, Illinois, USA,
20
Ohio State University, James
Comprehensive Cancer Center, Columbus, Ohio, USA,
21
Weill Cornell
School of Medicine, Medicine, New York, New York, USA,
22
Penn State
Cancer Institute, Neurosurgery, Hershey, Pennsylvania, USA,
23
Northwestern University Feinberg School of Medicine, Hematology/
Oncology, Chicago, Illinois, USA
Introduction: Treatment of older patients (pts) with PCNSL is chal-
lenging due to the prevalence of comorbidities, frailty, and effective
delivery of chemotherapy (CT). Optimal induction CT or consolida-
tion for older PCNSL pts are unknown. Moreover, there are a paucity
of large‐scale prognostication studies available. We analyzed post‐
induction treatment patterns and outcomes with prognostication
across 19 academic centers.
Methods: We conducted a large, RW retrospective study of newly
diagnosed PCNSL pts (1/2008‐1/2019) ages > 60 years (yrs). Among
525 older pts in the full data set (David KA et al, ASH 2020), 363 pts
achieved either complete or partial remission (CR/PR) with induction.
Survival rates were estimated by Kaplan‐Meier with differences
assessed by log rank test. Univariate associations were derived via
Cox model with variables p < 0.05 entered stepwise into multivariate
(MVA) models.
Results: Among 363 pts in PR or CR, mean age was 70 yrs (60‐88). 50
(14%) pts underwent consolidative autologous stem cell transplant
(ASCT), with mean age 66 yrs (60‐77) and ECOG PS 0‐1 in 72% ASCT
pts. 18 pts (mean age 68, range 62‐75) received consolidative radi-
ation therapy (RT). Post‐induction maintenance was given to 22% of
pts (mean age 72 yrs, 60‐86); the most common regimens were
temozolomide (28%), methotrexate (19%), and lenalidomide (25%).
Among all 363 pts, median progression‐free survival (PFS) was 61
months (95% CI 41‐72, Figure 1A) and median overall survival (OS)
was 70 months (95% CI 56‐90, Figure 1B).
In the full data set of 525 pts on MVA analysis, advancing
age & worse ECOG PS were associated with inferior PFS, while
advancing age, hypoalbuminemia, CIRS‐G score & worse ECOG PS
were associated with inferior OS. On MVA analysis among the 363
CR/PR pts, factors associated with inferior PFS were advancing
age (HR 1.050, p = 0.0004) and anemia (HR 1.13, p = 0.0228),
with advancing age (HR 1.057, p = 0.0006), impaired creatinine
clearance (1.009, p = 0.0381), and worse ECOG PS (p = 0.0049)
associated with inferior OS.
The 3‐yr PFS among pts undergoing ASCT was 72% vs. 46%
among those who did not (p = 0.002) with 3‐yr OS 81% vs. 64%,
respectively (p = 0.02); these survival improvements persisted when
stratified for the aforementioned prognostic factors (Figure 1C/D).
Among pts who received maintenance therapy, 3‐yr PFS was 65% vs.
44% with no maintenance (p = 0.02), with 3‐yr OS of 83% vs. 61%,
respectively (p = 0.0007)), with both remaining significant on strati-
fication (Figure 1E/F). Consolidative RT did not improve survival
(data not shown).
SUPPLEMENT ABSTRACTS
-
229
Conclusions: Collectively, older pts with PCNSL have suboptimal
outcomes, and improved therapy is needed. Among those with
response to induction, consolidative ASCT may improve outcomes,
although this constituted a minority of pts. Maintenance treatment
also appeared to improve outcomes. Future studies should focus on
optimal maintenance regimens for patients not fit for ASCT.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Extranodal
non‐Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
158 | PRIMARY CENTRAL NERVOUS SYSTEM POST‐
TRANSPLANT LYMPHOPROLIFERATIVE DISORDER (CNS‐PTLD):
A 20 YEARS RETROSPECTIVE SINGLE CENTER EXPERIENCE
N. Lang
1
, A. De la Torre
1
, R. Kridel
1
, A. Prica
1
, M. Crump
1
, V. Kukreti
1
,
J. Kuruvilla
1
, R. Tsang
1
, D. Hodgson
1
, D. Rodin
1
, S. Bhella
1
1
Princess Margaret Hospital, Haematology, Toronto, Canada
Introduction: Post‐transplant lymphoproliferative disorder (PTLD)
represent immunosuppression‐related lymphoid or plasmacytic pro-
liferation that occur in the setting of solid organ or hematopoietic cell
transplantation. Primary central nervous system involvement of
PTLD (CNS‐PTLD) is a rare manifestation, present in 10‐15% of all
cases. Prior studies demonstrated that CNS‐PTLD was associated
with renal transplantation, EBV virus reactivation, large B cell lym-
phoma morphology and the use of mycophenolate mofetil. We
present a single center retrospective analysis of CNS‐PTLD patient
outcomes over a 20‐year period.
Methods: We performed a retrospective chart review of patients
with CNS‐PTLD (defined as primary CNS lymphoma involvement at
diagnosis) at the Princess Margaret Cancer Centre from 2000‐2020.
Patient and disease characteristics, responses, and survival outcomes
were collected from the Lymphoma database and electronic patient
records with REB approval.
Results: Out of 183 PTLD patients we identified a total of 14 patients
(7.6%) with CNS‐PTLD were identified, all after solid organ trans-
plant, 57% were female, median age at diagnosis 47 years [21‐73],
64% had a renal transplant. Median time from transplant to PTLD
was 113 months [4.3‐337.3]. Thirty‐six percent presented with an
ECOG ≥ 2, 50% had an IPI score ≥ 3 and 86% had received myco-
phenolate mofetil as immunosuppression. Most patients were EBV
positive (92%), monomorphic (92%), diffuse Large B Cell Lymphoma
(71%), non‐germinal center subtype (80%), with a median prolifera-
tion index of 70% [50‐80].
Treatment of CNS‐PTLD was heterogenous. All had immuno-
suppression reduction, 21% of the patients received radiation alone,
58% chemo‐radiation (72% of them with rituximab), 21% chemo-
therapy alone (33% of them with rituximab), 35% of all treated pa-
tients had methotrexate containing regimens. Twenty‐nine percent
received further lines of therapy (n=4) and 1 patient underwent
autologous transplantation.
ORR to first line therapy was 50% (CR 21%, PR 29%), 1 patient
had stable disease and 29% (n=6) had progressive disease (n=4) or
died before response assessment (n=2). Of the four patients
FIGURE 1 Survival PFS (A) and OS (B) are depicted for older PCNSL pts with CR or PR after induction. Autologous SCT was associated
with improved PFS (C) and OS (D). Maintenance theraphy resulted in improved PFS (E) and OS (F). P values stratified on PFS for advancing age
and anemia and for advancing age and anemia and for advancing age, impaired creatinine, and worse ECOG performance status on OS
230
-
SUPPLEMENT ABSTRACTS
receiving salvage therapy, one achieved a CR, two a PR and one was
not evaluable for response.
7 deaths occurred, the majority within 3 months of diagnosis
(n=5), most from disease progression (n=4), all presenting an ECOG
≥2 at diagnosis. Median overall survival was 75.7 months.
Conclusions: Our cohort demonstrated that CNS involvement occurs
late after transplantation, frequently associated with EBV + mono-
morphic DLBCL subtype. In line with literature, mycophenolate
mofetil use was observed in the majority of cases. Despite the
aggressive nature of CNS‐PTLD, half of our cohort patients were able
to tolerate their initial treatment, achieved sustained response and a
prolonged survival.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Aggressive
T‐cell non‐Hodgkin lymphoma
No conflicts of interests pertinent to the abstract.
159 | PHASE IB/II STUDY OF LENALIDOMIDE, RITUXIMAB,
HIGH‐DOSE METHOTREXATE (R2‐MTX) REGIMEN, FOLLOWED
BY LENALIDOMIDE MAINTENANCE IN NEWLY DIAGNOSED
PRIMARY CNS LYMPHOMA
Y. Zhang
1
, W. Wang
1
, D. Zhao
1
, W. Zhang
1
, D. Zhou
1
1
Peking Union Medical College Hospital, Department of Hematology,
Beijing, China
Objective: Primary central nervous system lymphoma (PCNSL) is a
rare subtype of extranodal NHL with an aggressive clinical course
and poor outcomes. High‐dose methotrexate (HD‐MTX) based
regimen significantly improves the outcomes, but 10‐35% of patients
are treatment refractory. In this study, we evaluated the safety,
efficacy, and feasibility of lenalidomide, rituximab, and HD‐MTX (R2‐
MTX) regimen for newly diagnosed PCNSL patients.
Method: This is a multicenter prospective phase Ib/II study
(NCT04120350). Eligible patients had newly diagnosed PCNSL, age
≥18, and normal end‐organ function. The phase Ib study used the 3
+3 dose‐escalation design. Lenalidomide was dosed at 15mg daily
(day 1‐14) (level 1), 20mg daily (day 1‐14) (level 2) and 25mg daily
(day 1‐14) (level 3); rituximab was dosed at 375mg/m2 (d0), MTX was
dosed at 3.5g/m2 (d1) (all dose levels). Every 21 days were as a
course of treatment. R2‐MTX regimen was given for 6 cycles, then
lenalidomide (25mg daily, day 1‐21) at 28‐day cycles was given for a
maximum of 2 years as maintenance. In phase I study, dose‐limiting
toxicity (DLT) within the first 2 cycles was evaluated to determine
the recommended phase II dose.
Result: 17 patients were enrolled from August 2019 to December
2020: 10 patients in phase Ib (3, 4, 3 patients received LEN 15mg,
20mg, and 25mg, respectively); and 7 patients in phase II study.
No DLTs were observed in phase Ib study, and the recommended
phase II dose of lenalidomide was 25mg daily. The last follow‐up
was January 31
th
2021. 11(64.7%) pts were male and the me-
dian age was 60 (range 32‐74) . 13 patients were mediate and
high‐risk group according IELSG score(2‐5 points). Common grade
≥3 adverse events (AEs) of induction therapy were neutropenia
(41.2%), infection(5.9%), anemia (5.9%), thrombocytopenia (5.9%)
and acute kidney injury (5.9%) (all these AE occurred in one pa-
tient who suffered from MTX overdose); other AE (grade 1‐2, >
10%) were elevated ALT(47.1%), fatigue(29.1%), nausea/vomiting
(23.5%), numbness (23.5%), infection(11.8%), renal injury (11.8%)
and rash (11.8%). 16 patients were evaluable for response, and the
overall response rate (ORR) was 100%: 10 patients achieved
complete remission, and 6 patients achieved partial remission. The
median follow‐up time was 13.2 (1.3‐17.3) months, 4 patients
SUPPLEMENT ABSTRACTS
-
231
relapsed and 2 patients died for disease progression, the median
PFS was 13.3 months (Figure 1).
Conclusion: R2‐MTX regimen is a feasible and active combination
treatment for newly diagnosed PCNSL patients. It demonstrates an
excellent response rate, as well as good tolerability. More clinical
data will be updated from this ongoing study (NCTNCT04120350).
EA – previously submitted to EHA 2021.
Keywords: Immunotherapy, Aggressive B‐cell non‐Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
160 | USE OF METHOTREXATE, WHATEVER KIDNEY
FUNCTION, WITH A SIMPLE ALGORITHM, RADICALLY CHANGES
THE PROGNOSIS OF POST‐TRANSPLANT CNS LYMPHOMAS
S. Choquet
1
, A. Lavaud
1
, I. Boussen
1
, D. Roos‐Weil
1
, V. Morel
1
,
M. Uzunov
1
, S. Solorzano
1
, M. Le Garff
2
, v. Leblond
1
1
Pitie‐Salpetriere Hospital, APHP‐Sorbonne Universite, Clinical Hematol-
ogy, Paris, France,
2
Pitie‐Salpetriere Hospital, biological hematology, Paris,
France
Introduction: While systemic post‐transplant lymphoproliferations
(PTLDs) have a good prognosis, with a median survival of more than 6
years, PTLD of the central nervous system (CNS‐PTLD) have a very
poor prognosis with a CR rate of 38% and overall survival (OS) of 43%
at 3 years. The main prognostic criterion being the response to the first
line (Evens AM et al. Am J Transpl 2013), we hypothesized that the
majority of treatment failures were due to the absence or underuse of
the major drug in CNS NHL treatment, namely methotrexate (Mtx),
due to the high rate of renal failure in transplanted patients.
Patients and methods: Since April 2017, CNS‐PTLD treated at Pitie‐
Salpetriere Hospital, Paris, France, have been systematically treated
with a combination of methotrexate on day 1, Cytarabine on days 2
and 3, every 15 days for 6 cures. Cytarabine is given at 2g/m2/
d when the Creatinine clearance (cc) is >50ml/min, 1g/m2/d below.
The dose of Mtx of the first treatment is 100 mg/m2 in case of
dialysis or cc < 30 ml/min, between 100 and 500 mg/m2 for cc
between 30 and 50 ml/min, between 500 and 1000mg/m2 between
50 and 60 ml/min and/or albuminemia < 35g /L and/or >65 years,
3000mg/m2 in other cases. The dose of Mtx during the following
treatments depends on the dosage of Mtx at 24h: below 1 microM
the following dose is increased, above 5 microM it is reduced
otherwise it remains the same. The results are compared to those of
CNS‐PTLDs treated in the same unit before April 2017
Results: Of the 177 PTLDs treated since 1990 at Pitie‐Salpetriere
hospital, 47 are CNS‐PTLD, including 14 processed with the new
algorithm. The median age is 58 years, 9 patients have kidney or
kidney‐pancreas transplants, 2 heart, 1 lung and 2 liver, all are EBV
positive diffuse large B cell CNS‐PTLDs. The diagnosis is made in
median 88 months after the transplantation. The cc at diagnosis is in
median of 50 ml / min. Of these 14 patients, only 1 had a cc>60 ml/
min, and only one was able to receive 3000 mg/m2 of Mtx. The other
patients received between 200 and 1000 mg/m2 at the first treat-
ment, 6 had an increased dose during the next cycles following the
algorithm. No worsening of renal function or overdose of Mtx have
been rated. Of the 14 patients 13 achieved complete remission
(93%), 1 died of progression after the first cycle, 1 relapsed within 3
months and 1 after 1 year of CR. Median overall survival (OS) is not
achieved (239 days +). In comparison, of the 33 CNS‐PTLDs treated
before April 2017, 10 obtained a CR (30%), 6 a PR and the median OS
is 221 days, for the 9 CNS‐PTLDs treated without Mtx, only one
obtained a CR, 1 a PR and their OS is only 180 days
Conclusion: Contrary to general belief, methotrexate can be used
regardless of the renal function by adapting its dose to the cc then to
the dosages at H24. This new simple algorithm increased the CR rate
from 30% to more than 90% and improve OS. In case of confirmation
on further series, this new attitude should revolutionize the man-
agement of CNS‐PTLDs … but also other CNS‐NHLs in case of renal
failure
Keywords: Chemotherapy
Conflicts of interests pertinent to the abstract
S. Choquet
Consultant or advisory role: Roche, Celgene BMS, Takeda, Janssen,
Abbvie, Sanofi, Biogaran, Novartis, Atara, Accord Healthcare
232
-
SUPPLEMENT ABSTRACTS
161 | COMBINATION OF RITUXIMAB‐LENALIDOMIDE‐
IBRUTINIB IN RELAPSED/REFRACTORY PRIMARY CNS
LYMPHOMA: A COHORT STUDY OF THE LOC NETWORK
C. Houillier
1
, C. Moluçon‐Chabrot
2
, M.‐P. Moles
3
, L. Willems
4
, G.
Ahle
5
, A. Waultier
6
, L.‐M. Fornecker
7
, K. Hoang‐Xuan
8
, C. Soussain
9
1
Hôpital Pitié‐Salpêtrière, Neuro‐oncology, Paris, France,
2
CHU Clermont‐
Ferrand, Hematology, Clermont‐Ferrand, France,
3
CHU d'Angers, Hema-
tology, Angers, France,
4
Hôpital Cochin, Hematology, Paris, France,
5
Hospices Civils, Neurology, Colmar, France,
6
CHU de Nîmes, Hematology,
Nîmes, France,
7
Institut de Cancérologie de Strasbourg Europe, Hema-
tology, Strasbourg, France,
8
Hôpital Pitié‐Salpêtrière, Neuro‐oncology,
Paris, France,
9
Institut Curie, Hematology, Saint Cloud, France
Introduction: Previous phase II studies showed that ibrutinib (iLOC
study) and the combination of rituximab‐lenalidomide (REVRI study)
have an activity in R/R PCNSL. The triple combination rituximab‐
lenalidomide‐ibrutinib (R
2
I) has proved feasible in systemic DLBCL.
Methods: From 2019, R
2
I was proposed within the French LOC
network on PCNSL in poor prognosis immunocompetent patients
with heavily pretreated R/R PCNSL. We prospectively registered
these patients in our database and retrospectively analysed the
results.
Results: 14 patients (9 women, 5 men) met the selection criteria. 13
had a brain relapse and 1 a meningeal relapse of a brain lymphoma.
R
2
I was administrated after a median of 2 previous lines of
chemotherapy (range 1‐4). 11/14 patients were refractory to 1st line
treatment. 5/14 patients had previously received high‐dose chemo-
therapy with autologous stem cells transplantation (HCT‐ASCT). 11/
14 patients were refractory to the last treatment preceding R
2
I. At
the initiation of R
2
I, median age was 63 years (range 42‐77) and
median KPS was 75% (range 40‐90). 10 patients received rituximab
q21 days and lenalidomide 25 mg/D D1‐D10; 4 patients received
rituximab q28 days and lenalidomide 20 mg/D D1‐D21. Rituximab
dose was 375 mg/m
2
. Ibrutinib was administrated continuously at
560 mg/D. The patients received a median of 2 months of R
2
I (max 9
months, still ongoing). The best response was complete response (CR)
in 4 patients (29%), partial response (PR) in 4 patients (29%), stable
disease in 3 patients and progressive disease in 3 patients. Best
response was achieved in a median of 2.5 months (range 1‐4). 3
patients received a consolidation treatment (WBRT: N = 2, HCT‐
ASCT: N = 1) after R
2
I, and R
2
I served as bridge before CAR‐T cells
in 1 patient in relapse after ASCT. Those 4 patients were still alive at
6, 12, 16 and 13 months, respectively. With a median follow‐up of
10.7 months, 1‐year PFS and 1‐year OS were 40% and 53%,
respectively. Grade III‐IV reported adverse effects were: cutaneous
toxicity (N = 1), infections (N = 3), including one case of probable
cerebral aspergillosis, cardiac arythmia (N = 1), neutropenia (N = 3),
lymphopenia (N = 1). R
2
I was discontinued due to toxicity in 3/14
patients. There was no toxic death.
Discussion‐conclusion: Our cohort is distinguished by its high pro-
portion of chemorefractory patients (79%) compared to iLOC and
REVRI studies (27% and 16%, respectively). In this cohort of heavily
pretreated very poor prognostic R/R PCNSL, R
2
I combo resulted in a
rapid onset overall response in 8/14 patients, with manageable
toxicity. R
2
I allowed 4 patients to achieve CR/PR and proceed to
consolidation or CART‐cell therapy. Three patients are still on ther-
apy in CR≥6 months. R
2
I is currently being assessed in a prospective
trial (NCT033066130703167). The encouraging results of this small
retrospective cohort yet supports its use in R/R PCNSL failing con-
ventional chemotherapies.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Molecular
Targeted Therapies
No conflicts of interest pertinent to the abstract.
162 | CAR‐T CELL THERAPY IN PRIMARY CENTRAL NERVOUS
SYSTEM LYMPHOMA (PCNSL): THE EXPERIENCE OF THE
FRENCH NETWORK FOR OCULO‐CEREBRAL LYMPHOMAS (LOC)
M. Alcantara
1
, C. Houillier
2
, M. Le Garff‐Tavernier
2
, L. Souchet
2
,
D. Roos‐Weil
2
, V. Morel
2
, M. Uzunov
2
, C. Metz
2
, S. Nguyen‐Quoc
2
,
N. Jacque
2
, N. Gauthier
2
, M. Le Cann
2
, F. Norol
2
, L. Willems
3
,
A. Waultier Rascalou
4
, C. Salanoubat
5
, R. Fior
6
, M. Blonski
7
,
M.‐T. Rubio
7
, C. Soussain
8
, S. Choquet
2
1
Institut Curie, 75005, Paris, France,
2
Hôpital Universitaire Pitié‐
Salpêtrière, 75013, Paris, France,
3
Hôpital Cochin, 75014, Paris, France,
4
CHU de Nîmes, 30900, Nîmes, France,
5
Centre Hospitalier Sud
Francilien, 91106, Corbeil Essonnes, France,
6
Hôpital Antoine‐Béclère,
92140, Clamart, France,
7
Centre Hospitalier Régional et Universitaire de
Nancy, 54035, Nancy, France,
8
Institut Curie, 92210, Saint‐Cloud,
France
Introduction: Primary central nervous system lymphoma (PCNSL) is
mainly a diffuse large B cell lymphoma (DLBCL) with a non‐germinal
center B cell (non‐GCB) origin. Relapsed/refractory (R/R) PCNSLs are
associated with a poor prognosis and an unmet medical need.
Chimeric antigen receptor (CAR)‐T cells targeting CD19 demon-
strated remarkable efficacy, leading to their commercial approval for
R/R DLBCL, but no data are currently available for PCNSL.
Methods: The French network for oculo‐cerebral lymphomas (LOC)
database prospectively records all PCNSL cases from 32 French
centers. We retrospectively analyzed this national database in order
to collect all cases of R/R PCNSLs treated with commercially avail-
able CAR‐T cells. The main objective was to evaluate the safety and
efficacy of CAR‐T therapy in this setting.
Results: Between January 2020 and March 2021, we identified
9 patients with R/R PCNSL who received commercial anti‐CD19
CAR‐T cells (7 tisagenlecleucel and 2 axicabtagene ciloleucel). At
time of infusion, the median age was 67 years old (range, 48 – 75).
Eight patients had a brain parenchymal involvement, including one
with eye localization, and 1 had an isolated cerebrospinal fluid infil-
tration. The median number of prior therapies before leukapheresis
was 3 (2 – 5) and 4 patients had progressive disease at time of CAR‐T
infusion. All patients received a lymphodepleting chemotherapy
SUPPLEMENT ABSTRACTS
-
233
consisting of cyclophosphamide and fludarabine before CAR‐T infu-
sion. The median follow‐up was 2.4 months. Six patients experienced
cytokine release syndrome (CRS, any grade), including 1 patient with
CRS of grade 3 or higher. Immune cell‐associated neurotoxicity
syndrome (ICANS) of any grade occurred in 5 patients, including 2
patients with ICANS of grade 3 or higher. Four patients received
tocilizumab and corticosteroids. The overall response rate (ORR) at
1‐month was 62%, with 25% achieving a complete response (CR).
Best ORR and CR were 87% and 37% respectively. The overall sur-
vival is presented in Figure 1.
The updated results will be available and presented during the
2021 ICML meeting.
Conclusion: To our knowledge, this study represents the largest
cohort of patients treated with anti‐CD19 CAR‐T cells for R/R
PCNSL. Despite a short follow‐up, our results suggest that com-
mercial CAR‐T cells may be an efficient option to treat R/R PCNSL,
with no unexpected toxicity. Large clinical trials are needed to
confirm these encouraging results.
Keywords: Cellular therapies
Conflicts of interests pertinent to the abstract
M. Alcantara
Consultant or advisory role: Novartis, Janssen
S. Choquet
Consultant or advisory role: Novartis, Janssen, Roche, Celgène,
Takeda, Sandoz, Sanofi
163 | LENALIDOMIDE AND RITUXIMAB REGIMEN COMBINED
WITH INTRAVITREAL METHOTREXATE FOLLOWED BY
LENALIDOMIDE MAINTENANCE FOR PRIMARY VITREORETINAL
LYMPHOMA: A PROSPECTIVE PHASE II STUDY
Y. Zhang
1
, X. Zhang
2
, Dong‐m. Zou
1
, L. Zhang
3
, Mei‐f. Zhang
2
, D.
Zhou
1
, W. Zhang
1
1
Peking Union Medical College Hospital, Department of Hematology,
Beijing, China,
2
Peking Union Medical College Hospital, Department of
Ophthalmology, Beijing, China,
3
Peking Union Medical College Hospital,
Department of Clinical Laboratory, Beijing, China
Primary vitreoretinal lymphoma (PVRL) is a rare variant of primary
central nervous system (CNS) lymphoma, for which currently there are
no optimal treatment options. This prospective single‐center study
enrolled immunocompetent patients with newly diagnosed PVRL be-
tween August 2018 and January 2020. Patients received local and
systemic therapies: intravitreal methotrexate (MTX, 400 μg, 0.1 mL)
injections for 1 year (total 16 injections) and six cycles of the rituximab
(375 mg/m
2
on day 1) and lenalidomide (25 mg on day 1–21; R2)
regimen. Lenalidomide was maintained for 2 years in patients who had
achieved a response. We enrolled 11 patients with a mean age of 58
(range, 48–70) years, of which 10 achieved complete remission at the
first evaluation. The median follow‐up period was 18.3 (range, 10.6–
27.8) months, and the median progression‐free survival was 12.7
months. Moreover, a total of eight patients relapsed. The most com-
mon adverse event (AE) was neutropenia, which occurred in seven
patients (63.6%), followed by grade 3 ocular toxicities, including
cataract formation, in six patients (54%). These findings suggest that
the R2 regimen combined with intravitreal MTX, followed by lenali-
domide maintenance, is a safe option for PVRL with moderate efficacy.
This trial is registered with ClinicalTrials.gov (number NCT 03746223).
EA – previously submitted to EHA 2021.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Extranodal
non‐Hodgkin lymphoma, Immunotherapy
No conflicts of interest pertinent to the abstract.
164 | RITUXIMAB‐DOSE‐ADJUSTED EPOCH (R‐DA‐EPOCH) IN
PRIMARY MEDIASTINAL LARGE B‐CELL LYMPHOMA (PMLBCL):
REAL‐LIFE EXPERIENCE ON 190 PATIENTS FROM 3
MEDITERRANEAN COUNTRIES
T. Vassilakopoulos
1
, B. Ferhanoglu
2
, N. Horowitz
3
, Z. Mellios
4
,
L. Kaynar
5
, M. Zektser
6
, A. Symeonidis
7
, A. Piperidou
1
, C. Kalpadakis
8
,
O. M. Akay
9
, A. C. Atalar
9
, E. Katodritou
10
, T. Leonidopoulou
11
,
S. Papageorgiou
12
, T. Tadmor
13
, O. Gutwein
14
, S. Karakatsanis
15
,
C. Ganzel
16
, G. Karianakis
17
, G. Isenberg
3
, G. Gainaru
17
, E. Vrakidou
17
,
M. Palassopoulou
18
, M. Ozgur
19
, M. Siakantaris
1
, S. Paydas
20
,
FIGURE 1 Overall survival for the 9 R/R PCNSL patients
treated with anti‐CD19 CAR‐T cells
234
-
SUPPLEMENT ABSTRACTS
P. Tsirigotis
12
, M. Tsirogianni
21
, E. Hatzimichael
22
, T. Tuglular
23
,
C. Chatzidimitriou
1
, E. Megalakaki
24
, N. Kanellias
25
, P. Zikos
26
,
A. Koumarianou
27
, A. Gafter‐Gvili
28
, M. Angelopoulou
1
, T. Karmiris
4
,
R. Gurion
28
1
Department of Hematology and Bone Marrow Transplantation,
National and Kapodistrian University of Athens, Laikon General Hospital,
Athens, Greece,
2
Department of Hematology, American Hospital,
Istanbul, Turkey,
3
Hematology Institut, Rambam Medical Center, Haifa,
Israel,
4
Department of Hematology and Lymphoma, Evangelismos
General Hospital, Athens, Greece,
5
Department of Hematology, Erciyes
University, Kayseri, Turkey,
6
Department of Hematology, Soroka Medical
Center, Beer Sheba, Israel,
7
Hematology Division, Department of Internal
Medicine, University of Patras, Patra, Greece,
8
Department of
Hematology, University Hospital, University of Crete, Heraklion, Crete,
Greece,
9
Department of Hematology, Koc University, Istanbul, Turkey,
10
Department of Hematology, Theagenion Anticancer General Hospital,
Thessaloniki, Greece,
11
Department of Hematology, Sismanoglion
General Hospital, Athens, Greece,
12
Second Propedeutic Department of
Internal Medicine, National and Kapodistrian University of Athens,
ATTIKON General Hospital, Athens, Greece,
13
Department of
Hematology, Bnai Zion Medical Center, Haifa, Israel,
14
Hematology
Department, Shamir Medical Center, Be'erYa'akov, Israel,
15
Third
Department of Internal Medicine, National and Kapodistrian University
of Athens, Sotiria Hospital, Athens, Greece,
16
Department of
Hematology, Shaare Zedek Medical Center, Jerusalem, Israel,
17
Department of Hematology, HYGEIA Hospital, Athens, Greece,
18
Department of Hematology, University Hospital, University of Thessaly,
Larissa, Greece,
19
Department of Hematology, Kocaeli University,
Kocaeli, Turkey,
20
Department of Hematology, Cukurova University,
Adana, Turkey,
21
Department of Hematology and Bone Marrow
Transplantation, Saint Savvas Regional Cancer Hospital, Athens, Greece,
22
Department of Hematology, University of Ioannina, Ioannina, Greece,
23
Department of Hematology, Marmara University, Istanbul, Turkey,
24
Department of Hematology, METAXA Cancer Hospital, Athens,
Greece,
25
Department of Therapeutics, National and Kapodistrian
University of Athens, Alexandra Hospital, Athens, Greece,
26
Hematology
Department, General Hospital of Patras “Agios Andreas”, Patra, Greece,
27
Department of Hematology, METROPOLITAN Hospital, Athens,
Greece,
28
Department of Hematology, Rabin Medical Center,
PetachTikva, Israel
Background: Real‐life studies of moderate size have shown satis-
factory but less impressive results compared with the initial study of
R‐da‐EPOCH in PMLBCL. However, the strategies regarding the use
of consolidative radiotherapy (RT) and the compliance with the strict
instructions on dose escalation have not been studied.
Aim: To assess the clinical outcomes and prognostic factors after R‐
da‐EPOCH, the use of consolidative RT and protocol compliance in a
multinational real‐life setting.
Patients and Methods: 190 patients (≤60 years) were enrolled from
18 Greek (n = 109), 6 Israeli (n = 47) and 6 Turkish (n = 34) centers.
Consolidative RT was given at the treating physician's discretion and
was highly affected by PET/CT results.
Results: The median age of the patients was 33 years (16‐60), 117
(62%) were females, 35% had B‐symptoms, 31% extranodal
involvement (E or stage IV), 18% PS≥2, 84% elevated LDH (35%
highly elevated ≥2xnormal). The median follow‐up was 24 months
(1‐80). Among 179 patients evaluable for response (10 too early or
lost, one toxic death), 16 (9%) did not receive RT due to inadequate
response. Among 163 potentially eligible responders, RT was spared
in 140 (86%); 23 received RT mainly for Deauville 4 residuals. The 3‐
year Freedom From Progression (FFP) was 84%. However, 4 patients
developed therapy‐related (t‐) AML at 10.5‐22 months from treat-
ment initiation, while in 1
st
remission, and one Hodgkin lymphoma,
for a 2‐year event‐free survival of 81%, if considered as events. The
5‐year overall survival (OS) was 91% with 11 disease‐related deaths
(1 toxic). Protocol violations were common (53%), mainly consisting
of insufficient dose escalation despite the absence of prohibitive
toxicity. Among 154 patients with available data, 62% reached level
≥3 and 30% ≥4 (80% and 46% among those with strict protocol
adherence). The 3‐year FFP was 89% vs 83% for patients with strict
protocol adherence or not (p = 0.33); OS was not also different. FFP
did not differ according to the final level reached (≥3 or ≥4). A more
detailed analysis of outcome according to the degree of protocol
violations is currently ongoing. The prognostic systems including any
extranodal involvement and highly elevated LDH (≥2x) or bulk did
not significantly affect prognosis. However, patients with both risk
factors had 3‐year FFP rates 73‐76% and %‐year OS 75‐81%.
Conclusions/Discussion: In the largest series reported so far for R‐da‐
EPOCH in PMLBCL, FFP appeared somewhat but not impressively
better than the expected with R‐CHOP. However, consolidative RT
was safely omitted in >85% of responders mainly based on PET find-
ings. OS was >90%. However, the appearance of 4 cases of t‐AML
among 190 patients is worrisome. Significant dose‐escalation viola-
tions were recorded in the real‐life; their impact on outcomes appears
to be modest and is further evaluated in detail while the series is also
expanded with inclusion of even more patients.
Keywords: Chemotherapy, Combination Therapies, Aggressive B‐cell
non‐Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
165 | PRIMARY MEDIASTINAL B‐CELL LYMPHOMA:
INTENSIFIED REGIMENS DO NOT IMPROVE OUTCOMES AS
COMPARED TO RCHOP IN A RESOURCE‐CONSTRAINED
SETTING
R. D. Velasques
1
, W. F. Silva
1
, M. Bellesso
1
, V. Rocha
1
, J. Pereira
1
1
Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da
Universidade de São Paulo, Division of Hematology, São Paulo, Brazil
Introduction: Primary Mediastinal B‐cell Lymphoma (PMBCL) com-
prises less than 4% of non‐Hodgkin lymphomas. Despite R‐
DAEPOCH has been the upfront regimen of choice over R‐CHOP
plus radiotherapy (RT), the optimal treatment of PMBCL remains
SUPPLEMENT ABSTRACTS
-
235
undefined and outcomes in low and middle incomes countries are still
unknown. In this retrospective chart‐review study, we analyzed
characteristics and risk factors for response and survival of patients
with PMBCL treated with 3 different regimens, at a public health
university cancer center.
Methods: Patients with PMBCL diagnosed between 2008 ‐ 2018
eligible to intensive treatment were included. Some patients received
a modified outpatient regimen named ‘R‐CHOEP’. Treatment
response was based on the original radiology reports (CT or PET‐CT,
according to Cheson and Lugano criteria, respectively).
Results: A total of 95 patients were included. Median age was 28 years
(15‐74), 59.1% female. Most patients had localized disease (57.1%),
with 31.9% presenting extranodal disease. Bulky disease was found in
92.1% and thromboembolic event in 37%. R‐DAEPOCH (42%), R‐
CHOP (36%) and R‐CHOEP (22%) comprised the upfront regimen.
Cytoreductive chemotherapy was administered in 50%. Apart from a
higher mean LDH level in R‐DAEPOCH subset, patient's baseline
features were not statistically different. Interim assessment after four
courses showed 40%, 55.7% and 4.5% of complete response (CR),
partial response (PR) and progressive disease (PD) rates, respectively.
RT was performed in 42.1% of R‐DAEPOCH, 75% of R‐CHOP and 83%
of R‐CHOEP (p = 0.002). Patients in PR who received consolidation RT
achieved CR in 73.7%, while all patients in stable disease/PD eventu-
ally relapsed after RT. At the end of the treatment, metabolic CR rate
was 56.8% and PD was observed in 11.1%. Estimated 5‐year PFS and
OS were 77.2% and 77.4%, respectively. Interim imaging was predic-
tive of CR (p = 0.017). CR rate did not correlate with any baseline
feature or the frontline regimen – R‐DAEPOCH 74.3%, R‐CHOP 76.7%
and R‐CHOEP 82.3% (p = 0.089). In multivariable analysis, only LDH
levels remained independently associated with PFS (HR = 3.1, p =
0.02). Cumulative incidence of relapse at 5 years was not statistically
different according to treatment: R‐DAEPOCH (13.2%), R‐CHOP (6%),
R‐CHOEP (11.1%) (p = 0.71).
Conclusion: Despite the limited number of patients and the retro-
spective nature of the study, there was none statistically difference in
outcomes between a more intensified inpatient and conventional
outpatient regimens. Patients with less than PR did not benefit from
consolidative radiotherapy. In a resource‐constrained setting, where
a 4‐day inpatient chemotherapy infusion could be logistically prob-
lematic, this study points that R‐CHOP, as upfront treatment of
FIGURE 1 Survival probability according to upfront regimens
236
-
SUPPLEMENT ABSTRACTS
PMBCL, may be still safely adopted. Further studies on toxicity and
economic costs are needed.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
AGGRESSIVE NHL
166 | HIGH ADIPOSE TISSUE DENSITY IS A NEGATIVE
PROGNOSTIC FACTOR IN DLBCL PATIENTS TREATED BY R‐
CHOP, INDEPENDENT FROM TMTV AND PS –FROM THE
REMARC STUDY
J.‐F. Deux
1
, M. Meignan
2
, L. Chartier
3
, A. Judet
4
, L. Vercellino
5
, O.
Casasnovas
6
, V. Baud
7
, H. Tilly
8
, A.‐S. Cottereau
9
, C. Thieblemont
4
1
APHP, Hopital Henri Mondor, Radiologie, Creteil, France,
2
LYSA‐IM,
Hopital Henri Mondor, LYSA‐IM, Paris, France,
3
LYSARC, Statistique,
Pierre‐Benite, France,
4
APHP, Saint‐Louis Hospital, Hemato‐oncology,
Paris, France,
5
APHP, Hopital Saint‐Louis, Medecine Nucleaire, Paris,
France,
6
CHU le Bocage, Hematologie, Dijon, France,
7
Université de Paris,
NF‐KappaB, différenciaation et Cancer, Paris, France,
8
Centre Henri
Becquerel, INSERM U1245, Rouen, France,
9
APHP, Hopital Cochin,
Medecine Nucleaire, Paris, France
Background: Body mass composition (BMC) including body mass
index (BMI), muscle and adipocyte tissue structure has been reported
to be associated with survival in oncological patients (pts). The aim
was to analyze the prognostic impact of the BMC in elderly pts with
diffuse large B‐cell lymphoma treated with R‐CHOP in first line.
Patients and Methods: Pts included in the REMARC study
(NCT01122472), (DLBCL >60 to 80 years old, responder to R‐CHOP
randomized between lenalidomide or placebo). BMC parameters
were measured at the level of L3 with an Artificial Intelligence
software on the CT part of the baseline PET/CT performed before
treatment: lumbar skeletal muscle index (LSMI, cm
2
/m
2
) and density
(LSMD, Hounsfield Unit (HU)), lumbar psoas muscle index (LPMI) and
density (LPMD), lumbar subcutaneous adipose index (LSAI) and
density (LSAD), and lumbar visceral adipose index (LVAI) and density
SUPPLEMENT ABSTRACTS
-
237
(LVAD). The optimal body parameters cut‐offs for PFS and OS were
determined by X‐tile analyses and confirmed by a training validation
method.
Results: 289 pts were analyzed, including 171 males (59.2%) and 113
(39.1%) pts≥70. In male, BMC showed significant higher BMI LSMI
LPMI, and LVAI. In pts ≥70, BMC showed significant lower LSMI and
higher LVAI than in pts < 70. In univariate analysis, only adipose
densities (LSAD and LVAD) were prognostic of outcome.
Pts with high LSAD (>‐90 HU, n = 69, 24%) had a 3‐year PFS of
57.1% vs 77.8% (HR = 2.39 (95%CI = 1.5‐3.7)) and OS of 70.0% vs
90.4% (HR = 2.77 (95%CI = 1.6; 4.8)) for the low LSAD pts (≤‐90HU).
They had lower weight, BMI, worse ECOG PS (≥2, 26.1% vs 12.3%,
p = 0.012), more extranodal sites (≥2, 75.4% vs 45%, p < 10
‐3
),
higher TMTV (median of 327 cm
3
vs 211 cm
3
, p = 0.009), and higher
IPI (IPI 3‐5, 85.5% vs 66.4%, p = 0.002) and NCCN‐IPI (high/high‐
intermediate, 84.1 vs 63.7%, p = 0.010), but no difference in age (p =
0.24) or sex (p = 0.26).
Pts with high LVAD (>‐86 HU, n = 108, 37.4%) had a 3‐year PFS
of 63.1% vs 78.5% (HR = 1.92 (95%CI = 1.3; 2.9)) and OS of 75.4% vs
91.4% (HR = 2.66 (95%CI = 1.5;4.6)), lower weight, BMI, more
extranodal sites (≥2, 61.1% vs 47%, p = 0.021), more bone marrow
involved (25.9% vs 13,3%, p = 0.026), higher TMTV (median of 306
cm
3
vs 207 cm
3
, p = 0.017), and higher NCCN‐IPI (high/high inter-
mediate, 79.6% vs 61.9%, p = 0.010), and no difference in age (p =
0.19) or sex (p = 0.27).
Mutivariable analysis including densities, TMTV and ECOG
showed that LSAD(>‐90) and TMTV (>220cm
3
) were independent
predictors of PFS and OS and LVAD TMTV (>220cm3) and ECOG
(≥2) were independent predictors of PFS and OS .
Conclusions: This is the first report showing that adipose tissue
alteration is a strong prognosticator of outcome in DLBCL. The key
question remains if this adipose tissue alteration should be considered
as an inherent pt's frailty or would be a consequence of metabolic
changes induced by the tumor. Metabolomic analysis of the baseline
plasma is ongoing and might give us new insights into this question.
Keywords: Diagnostic and Prognostic Biomarkers
Conflicts of interests pertinent to the abstract
C. Thieblemont
Honoraria: Celgene, Kyte/Gilead, Novartis, Roche, Incyte
Research funding: Roche, Hospira
167 | LYMFOREST‐25: PERSONALLY‐TAILORED SURVIVAL
PREDICTION OF PATIENTS WITH DIFFUSE LARGE B‐CELL
LYMPHOMA USING CLINICO‐GENOMIC PROGNOSTIC MODELS
A. Mosquera Orgueira
1
, M. Cid López
1
, A. Peleteiro Raindo
1
,
J. Án. Díaz Arias
1
, M. S. González Pérez
1
, B. Antelo Rodríguez
1
,
L. Bao Pérez
1
, R. Ferreiro Ferro
1
, C. Aliste Santos
1
, M. M. Pérez
Encinas
1
, M. F. Fraga Rodríguez
1
, Z. Xu‐Monette
2
, C. Visco
3
,
K. Young
2
, J. L. Bello López
1
1
University Hospital of Santiago de Compostela, Hematology,
SANTIAGO DE COMPOSTELA, Spain,
2
Duke University Medical
Center, Pathology, Durham, USA,
3
University of Verona, Medicine,
Verona, Italy
Diffuse Large B‐cell Lymphoma (DLBCL) is the most frequent type of
lymphoma. Despite its high cure rate, 30–40% of cases exhibit
relapsed or refractory disease which frequently precludes a dismal
prognosis. For this reason, new therapies are being actively investi-
gated for the treatment of DLBCL, such as polatuzumab vedotin and
CAR‐T therapies. As new drugs are developed, it becomes increas-
ingly important to provide patients with an optimal prediction about
the expected outcome of treatment with R‐CHOP. Today, clinical
risk stratification of DLBCL is still based on the International Prog-
nostic Index (IPI) and its variants. Recently, we demonstrated the
feasibility of applying machine learning on gene expression and
clinical data to make individual predictions about DLBCL patient
outcome.
Our objective was to reproduce the clinico‐genomic survival
model developed by our team and to refine its predictive capacity by
including new clinical and biochemical variables. For this purpose, we
used data from the International DLBCL Rituximab‐CHOP Con-
sortium Program Study. Gene expression was data was rank‐
normalized, and the database was randomly split in a training
(80%) and validation (20%) group. Afterwards, we created random
forests models of survival using the same set of variables that we
reported in our previous report, reaching C‐indexes >0.66 in all
cases, which indicate good discrimination capacity.
In a second step, we included the following data in order to refine
the precision of the model: IPI score, ECOG, high LDH, age at diag-
nosis, Ann‐Arbor stage, number of extranodal sites affected, bulky
disease, cell‐of‐origin (COO) status and the percentage of cells pos-
itive for CD10, BCL6, FOXP1, GCET and MUM1. We created random
forests with and without resampling and with 10 different values of
the nsplit variable, and variables with low importance were itera-
tively removed. The best model was selected for variable optimiza-
tion and further reduction, reaching c‐indexes of 0.762 and 0.731 in
the training and validation sets. This model included 25 variables,
including 19 transcripts, and was named LymForest‐25. Importantly,
the model excluded COO status from the classification. A graphical
representation of LymForest‐25 survival predictions and real patient
outcomes clearly indicates the capacity of this tool to stratify patient
risk (Figure 1). Furthermore, LymForest‐25 outperformed the pre-
dictive capacity of the IPI score, all individual IPI variables, Bulky
disease and COO status.
In comparison with other tools, LymForest‐25 has the advantage
of making individualized predictions that do not reside in pre‐
established clinical and molecular subgroups, overcoming the limi-
tations of imperfect patient subgrouping scores. Such an approach
could drive the development of new first‐line therapeutic in-
terventions for selected high‐risk patients based on personalized
predictions.
238
-
SUPPLEMENT ABSTRACTS
FIGURE 1 (A‐B) DLBCL patients outcome according to the predicted 1 year survival quartiles created by LymForest‐25 in both the
training and validation sets. (C‐D) Survival outcomes according to the predicted 5 year survival medians created by LymForest‐25 in patients
with IPI scores <=3 in the training and validation sets, respectively. (E‐F) Survival outcomes according to the predicted 5 year survival medians
created by LymForest‐25 in patients with IPI scores >3 in the training and validation sets, respectively
SUPPLEMENT ABSTRACTS
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239
Keywords: Diagnostic and Prognostic Biomarkers, Aggressive B‐cell
non‐Hodgkin lymphoma, Chemotherapy
Conflicts of interests pertinent to the abstract
A. Mosquera Orgueira
Consultant or advisory role: Janssen, AstraZeneca
Honoraria: Janssen, Amgen
Research funding: Celgene, Roche, Abbey, Janssen
Educational grants: Janssen, Celgene, Pfizer
168 | PROGNOSTIC SIGNIFICANCE OF TIME FROM LAST
THERAPY IN PATIENTS WITH DIFFUSE LARGE B‐CELL
LYMPHOMA: RETROSPECTIVE ANALYSIS OF ELECTRONIC
HEALTH RECORDS AND CLAIMS DATA IN THE US
M. Matasar
1
, F. Castro
2
, Y. Liu
3
, A. Abraham
3
, Y. Oki
4
, M. Dickinson
5
1
Memorial Sloan Kettering Cancer Center, Department of Medicine, New
York, New York, USA,
2
F. Hoffmann‐La Roche Ltd, Real World Data
Science ‐ Oncology, Basel, Switzerland,
3
Genesis Research, Hoboken, USA,
4
Genentech, Inc., Product Development Oncology, South San Francisco,
USA,
5
The Peter MacCallum Cancer Centre, Royal Melbourne Hospital
and The University of Melbourne, Clinical Haematology, Melbourne,
Australia
Introduction: Primary refractory diffuse large B‐cell lymphoma
(DLBCL) is a major clinical challenge; poor outcomes in patients (pts)
with primary refractory DLBCL were reported in the SCHOLAR‐1
study (Crump, et al. Blood 2017). A limited number of studies have
evaluated real‐world outcomes of pts with primary refractory DLBCL
in the broader healthcare setting. Using real‐world data, we describe
outcomes of pts with DLBCL receiving second‐line (2L) therapy, ac-
cording to time from last treatment (TLT; defined as time from end of
first‐line [1L] to start of 2L therapy).
Methods: We used the nationwide Flatiron Health (FH) electronic
health record‐derived de‐identified database and the Surveillance,
Epidemiology, and End Results (SEER)‐Medicare (SEER‐M)‐linked
database, which combines the SEER Cancer Registry and Medicare
claims database. Data of pts with DLBCL who received 2L therapy
between Jan 2011–Jan 2020 in FH, and Jan 2011–Dec 2015 in
SEER‐M, were reviewed. Pts aged ≥18 years (>65 years in SEER‐
M) with DLBCL, who received cyclophosphamide‐ and doxorubicin‐
containing 1L regimens were included for analysis. For SEER‐M, all
pts enrolled in fee‐for‐service Medicare were required to have
complete claims. Data of pts who developed a secondary malig-
nancy were censored at the time of the malignancy. Medical re-
view of treatment regimens was performed for the final cohorts.
Pts were grouped into categories of TLT (<6 mo, 6–12 mo, and
>12 mo), and the impact of TLT was analyzed for association with
overall survival (OS), defined as time from start of salvage therapy
to death.
Results: Overall, 866 pts were included (FH: n = 442; SEER‐M: n =
424) for analysis. Pt characteristics were similar between the co-
horts, except median age at diagnosis (FH: 65 years; SEER‐M: 74
years). Pts were mostly white (FH: 72.9%; SEER‐M: 91.5%), male (FH:
63.1%; SEER‐M: 52.1%), with Stage III–IV disease (FH: 64.9%; SEER‐
M: 69.5%). The most common 2L regimens were rituximab (R) +
ifosfamide + carboplatin + etoposide (FH: 39.8%; SEER‐M: 7.5%), R +
bendamustine (FH: 14.0%; SEER‐M: 29.2%), and R + gemcitabine +
oxaliplatin (FH: 8.4%; SEER‐M: 12.5%). Using a TLT cut‐off of <6 mo,
236 (53.4%) pts in FH and 197 (45.3%) pts in SEER‐M were classified
as primary refractory. In the FH cohort, median OS for TLT < 6 mo,
6–12 mo, and >12 mo were 9.1 mo (95% confidence interval [CI]:
8.1–13.1 mo), 20.9 mo (95% CI: 13.7–47.5), and 42.9 mo (95% CI:
22.8–57.3), respectively. In the SEER‐M cohort, median OS for TLT <
6 mo, 6–12 mo, and >12 mo were 8.6 mo (95% CI: 6.7–11.4), 11.7 mo
(95% CI: 8.8–16 .1), and 18.9 mo (95% CI: 15.7–32.9), respectively
(Figure).
Conclusions: This analysis highlights the poor outcomes of pts with
shorter TLT, particularly those with primary refractory DLBCL (TLT <
6 mo). Novel therapies are needed for this high‐risk pt population,
and future studies of 2L therapy should stratify enrollment by TLT to
control for this source of confounding.
EA – previously submitted to EHA 2021.
The research was funded by: F. Hoffmann‐La Roche Ltd/Genentech,
Inc. Third‐party editorial assistance, under the direction of the authors,
was provided by Carla Smith, MSc, of Ashfield MedComms, an Ashfield
Health company, and funded by F. Hoffmann‐La Roche Ltd.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
M. Matasar
Consultant or advisory role: Genentech, Inc., Bayer, Merck, Juno
Therapeutics, F. Hoffmann‐La Roche Ltd, Teva, Rocket Medical,
Seattle Genetics, Daiichi Sankyo, Takeda
Stock ownership: Merck
Honoraria: Genentech, Inc., F. Hoffmann‐La Roche Ltd, Glax-
oSmithKline, Bayer, Pharmacyclis, Janssen, Seattle Genetics, Immu-
novaccine Technologies, Takeda
Research funding: Genentech, Inc., F. Hoffmann‐La Roche Ltd, Glax-
oSmithKline, IGM Biosciences, Bayer, Pharmacyclis, Janssen, Rocket
Medical, Seattle Genetics, Immunovaccine Technologies
Educational grants: Genentech, Inc., F. Hoffmann‐La Roche Ltd,
Seattle Genetics, Bayer
F. Castro
Employment or leadership position: F. Hoffmann‐La Roche Ltd
Y. Liu
Employment or leadership position: Genesis Research
A. Abraham
Employment or leadership position: Genesis Research
240
-
SUPPLEMENT ABSTRACTS
Y. Oki
Employment or leadership position: F. Hoffmann‐La Roche Ltd/
Genentech, Inc.
Stock ownership: F. Hoffmann‐La Roche Ltd/Genentech, Inc.
M. Dickinson
Consultant or advisory role: F. Hoffmann‐La Roche Ltd, Novartis,
Bristol‐Myers Squibb, Gilead Sciences, Janssen
Honoraria: F. Hoffmann‐La Roche Ltd, Amgen, MSD, Janssen, Bristol‐
Myers Squibb, Novartis, Research funding: Novartis, F. Hoffmann‐La
Roche Ltd, Takeda, Celgene, MSD, Educational grants: F. Hoffmann‐
La Roche Ltd
Other remuneration: Speakers' Bureau: Novartis
169 | A SINGLE BLOOD TEST IS ABLE TO CLASSIFY DLBCL
PATIENTS IN THREE PROGNOSTIC CLUSTERS AT DIAGNOSIS
F. Martín Moro
1
, J. Marquet Palomanes
1
, A. González Rodríguez
1
, I.
Delgado Trillo
2
, C. López
2
, F. Herrera
2
, J. Villarrubia Espinosa
1
, G.
Moreno Jiménez
1
, J. A. García Vela
2
, F. J. López Jiménez
1
1
Hospital Universitario Ramón y Cajal, Hematology Department, Madrid,
Spain,
2
Hospital Universitario de Getafe, Hematology Department,
Madrid, Spain
Introduction: The prognostic impact of laboratory variables has
widely been studied in DLBCL, with variable results in literature.
Some studies included heterogeneous cohorts with different sub-
types of large cell lymphomas. Our aim was to evaluate the outcome
impact of relevant laboratory variables with different cut‐offs in a
homogeneous DLBCL series, and to construct an easily applicable
prognostic model.
Methods: Retrospective research of de novo DLBCL not other-
wise specified cases (2013‐2020 period) with a single and com-
plete blood test at diagnosis (n = 126). The laboratory variables
analysed were lactate dehydrogenase (LDH), albumin, beta‐2
microglobulin (β2M), haemoglobin (Hb), platelets, neutrophils,
lymphocytes, monocytes, lymphocyte to monocyte ratio (LMR),
neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte
ratio (PLR). The cut‐offs were chosen based on ROC curves for
both event‐free survival (EFS) and overall survival (OS), previ-
ous literature, and Institutional Laboratory ranges. The EFS and
OS univariate hazard ratio (UV HR) was analysed by Cox
regression model to assess the prognostic impact of each variable
and its cut‐offs, choosing the most relevant ones to construct the
model. The score of each variable was assigned according to the
median HR between EFS and OS (HR < 3:1 point; HR ≥3: 2
points). Three clusters were created according to the prognostic
impact of each point level (0‐7 points) and graphed by Kaplan
Meier curves.
Results: The cohort consisted of 64 females and 62 males, median
age 70 years (28‐89). The median follow‐up of the series was 29
months (0.3‐97). In Figure 1 is presented by forest plots the UV
HR of the laboratory variables with different cut‐offs for EFS and
OS. The variables included in the model were LDH >235 U/L (1
point. EFS HR 2.5 p = 0.008, OS HR 2.3 p = 0.02), β2M >4 mg/L
(2 points. EFS HR 3.9 p < 0.001, OS HR 5.1 p = <0.001), Hb <
120 g/L in females and <135 g/L in males (2 points. EFS HR 3 p =
0.001, OS HR 3.1 p = 0.001), platelets < 150,000/μL (1 point. EFS
OS from start of 2L treatment according to TLT category in (A)FH and (B)SEER‐M
SUPPLEMENT ABSTRACTS
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241
242
-
SUPPLEMENT ABSTRACTS
HR 1.9 p = 0.06, OS HR 2 p = 0.04), and NLR >4 (1 point. EFS HR
1.7 p = 0.06, OS HR 3.3 p < 0.001). The albumin level was
excluded because of its lack of significant impact on EFS. Cases
were divided into three clusters with different outcome (Figure 1):
0 points (n = 22; 3‐year EFS 88%, 3‐year OS 93%), 1‐3 points (n =
55; 3‐year EFS 65%, 3‐year OS 72%), and 4‐7 points (n = 49; 3‐
year EFS 34%, 3‐year OS 39%).
Conclusions: Here is presented a prognostic model based on
five laboratory variables (LDH, β2M, Hb, platelets, and NLR)
routinely evaluated at DLBCL diagnosis. The model is easily
applicable and allows to separate patients in three clusters with
well differentiated EFS and OS. Although the model would not
have therapeutic implication, it may allow clinicians to have pre-
liminary information on the prognosis of DLBCL patients by a
single blood test. Our purpose is to prospectively validate the
model in a larger cohort.
Keywords: Diagnostic and Prognostic Biomarkers, Aggressive B‐cell
non‐Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
170 | FINDING A CONCORDANT OR DISCORDANT BONE
MARROW INVOLVEMENT BY HISTOLOGY OR FLOW
CYTOMETRY AT DLBCL NOS DIAGNOSIS IMPLIES A WORSE
PROGNOSIS WHEREAS PET‐FDG DOES NOT
F. Martín Moro
1
, J. Marquet Palomanes
1
, I. Delgado Trillo
2
,
M. Piris Villaespesa
1
, C. López
2
, F. Herrera
2
, E. Rodríguez Martín
3
,
A. Martínez Lorca
4
, M. García‐Cosío Piqueras
5
, E. Roldán
Santiago
3
, J. A. García Marco
6
, F. J. López Jiménez
1
, J. A. García
Vela
2
1
Hospital Universitario Ramón y Cajal, Hematology Department,
Madrid, Spain,
2
Hospital Universitario de Getafe, Hematology
Department, Madrid, Spain,
3
Hospital Universitario Ramón y Cajal,
Immunology Department, Madrid, Spain,
4
Hospital Universitario Ramón
y Cajal, Nuclear Medicine Department, Madrid, Spain,
5
Hospital
Universitario Ramón y Cajal, Pathology Department, Madrid, Spain,
6
Hospital Universitario Puerta de Hierro, Hematology Department,
Madrid, Spain
Introduction: The prognostic value of bone marrow (BM) involve-
ment at DLBCL diagnosis when detected by PET is controversial.
The BM biopsy (BMB) analysis has outcome implication, whilst
flow cytometry (FCM) has scarcely been studied in this setting. It
is reported that a concordant large B cell infiltration associates a
worse prognosis, whereas a discordant involvement does not alter
the outcome (before WHO2016). Our aim was to analyse the
prognostic value of BM involvement detected by PET, BMB or
FCM in a homogeneous cohort of de novo DLBCL not otherwise
specified (NOS).
Methods: Retrospective two‐center research of de novo DLBCL
NOS cases (2013‐2020 period) with a complete BM assessment –
PET, BMB and FCM – at diagnosis (n = 103). BM samples were
non‐suitable for BMB and FCM analysis in 2 and 4 cases,
respectively. Clinical and biological characteristics of the cohort
were analysed and compared (descriptive statistics) according to
BM infiltration by each technique. Survival outcome was evaluated
by log rank test and Cox regression model, using Kaplan Meier
estimator for graphical representation.
Results: BM infiltration was demonstrated in 25/103 patients by
PET, 15/101 by BMB and 16/99 by FCM. A 16% of cases with
BM involvement by any technique presented infiltration by all of
them. The PET pattern was focal in 13/25 cases (52%), diffuse in
10/25 (40%) and both in 2/25 (8%). A concordant infiltration was
seen in 10/15 cases by BMB (67%) and 4/16 by FCM (25%),
whereas 3/15 (20%) and 11/16 (69%) presented a discordant
indolent involvement by BMB and FCM, respectively. Both
concordant and discordant patterns were seen in 2/15 cases by
BMB (13%) and 1/16 by FCM (6%). Figure 1 presents event‐free
survival (EFS) and overall survival (OS) analysis regarding each
technique (median follow‐up 29 months, 0.3‐97). Neither focal nor
diffuse PET patterns were related with outcome (1A). Both
concordant and discordant infiltration by BMB were associated
with a worse EFS, whereas the statistical difference was not
reached for OS (1B). Both concordant and discordant infiltration
were associated with a worse EFS and OS when assessed by FCM
(1C). No technique maintained statistically prognostic significance
in multivariate analysis. In patients with stage IV there was no
difference in EFS or OS if BM was infiltrated by each technique,
except for a higher OS in patients with PET+ vs PET‐ (HR 0.3, CI
95% 0.1‐0.9).
Conclusions: The coincidence between techniques for assigning
BM involvement at DLBCL NOS diagnosis was low. BM infiltration
by PET has no prognostic implication, whereas cases with positive
BMB or FCM present a worse prognosis regardless of concordant
or discordant infiltration. This data suggests that BMB should not
be abandoned, and FCM should be considered especially for
detection of indolent infiltration. Molecular assays are needed to
establish the clonal relationship between original tissue and BM in
DLBCL.
Keywords: Tumor Biology and Heterogeneity, Diagnostic and
Prognostic Biomarkers, Aggressive B‐cell non‐Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
SUPPLEMENT ABSTRACTS
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243
244
-
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171 | INTERIM PET/CT PREDICTS OUTCOMES OF DIFFUSE
LARGE B‐CELL LYMPHOMA (DLBCL) TREATED WITH FRONTLINE
LENALIDOMIDE/RCHOP (R2CHOP): LONG‐TERM ANALYSIS OF
MC078E
S. Desai
1
, B. Laplant
2
, W. Macon
3
, J. Young
4
, R. King
3
, Y. Wang
5
,
D. Inwards
6
, I. Micallef
6
, P. B. Johnston
6
, L. F. Porrata
6
, S. M. Ansell
6
,
T. M. Habermann
6
, T. E. Witzig
6
, G. S. Nowakowski
6
1
Mayo Clinic, Division of Hematology, Department of Medicine, Rochester,
Minnesota, USA,
2
Mayo Clinic, Department of Quantitative Health
Sciences, Rochester, Minnesota, USA,
3
Mayo Clinic, Department of
Laboratory Medicine and Pathology, Rochester, Minnesota, USA,
4
Mayo
Clinic, Division of Nuclear Medicine, Department of Radiology, Rochester,
Minnesota, USA,
5
Mayo Clinic, Division of Hematology, Department of
Medicine, Rochester, Minnesota, USA,
6
Mayo Clinic, Division of
Hematology, Department of Medicine, Rochester, Minnesota, USA
Introduction: Evaluating prognostic impact of interim (after 2 cycles
of therapy) 18F‐fluorodeoxyglucose positron emission tomography‐
computed tomography (iPET/CT), is important for clinical trials of
risk adapted therapies in treatment‐naïve (TN) DLBCL. Studies
evaluating iPET/CT have heterogenous methodologies and treatment
regimens producing conflicting results. A prospective study of a
uniformly treated and followed patients under a standardized pro-
tocol would accurately identify predictive value of iPET/CT in TN
DLBCL. Here we report outcomes by iPET/CT from a phase 2 trial of
lenalidomide, rituximab, cyclophosphamide, doxorubicin, vincristine
and prednisone (R2CHOP) in TN DLBCL (MC078E, NCT00670358).
Methods: Adult patients (pts) with untreated stage II‐IV DLBCL
and measurable disease were enrolled. Pts with central nervous
system involvement, recurrent venous thromboembolism (VTE), or
inability to take 81 mg daily aspirin were excluded. Pts received 6
cycles of R2CHOP which consisted of standard doses of R‐CHOP
and lenalidomide 25 mg daily on days 1‐10 of 21‐day cycles. All
pts received aspirin 81 mg for VTE prophylaxis. Pts underwent
PET/CT at baseline, interim and after cycle 6. PET/CT were
analyzed with 5‐point Deauville Score (DS). Negative PET/CT was
defined as DS of 1‐3 and positive PET/CT was defined as DS of 4‐
5. Primary endpoint was progression free survival (PFS) at 24
months. Secondary endpoints were overall response rates (ORR),
complete response (CR) rate, event‐free survival (EFS) and overall
survival (OS).
Results: 138 pts were accrued and 118 were eligible for MC078E.
104 pts who had iPET/CT (102 before cycle 3, 1 before cycle 2 and 1
before cycle 4) were included in this analysis. Median age was 64 (19‐
87) years at diagnosis. 61% were male, 86% had stage III‐IV, 45% had
IPI 3‐5. 92 (89%) completed 6 cycles of therapy and all received at
least 2 cycles. 58 had negative iPET/CT and 46 had positive iPET/CT.
Overall, 103 (99%, CI
95
: 94.8 ‐ 100) responded; 90 (87% (CI
95
: 78.4 ‐
92.4)) had CR. 73 (70%) were alive and progression‐free at 2 years. 2‐
year EFS, PFS and OS were 71% (CI
95
62.7‐80.3), 73.9% (CI
95
65.8‐
82.8) and 88.3% (CI
95
82.4‐94.8), respectively. In landmark analyses
from time of iPET/CT, patients who had positive iPET/CT had
significantly lower 2‐year EFS (49.6%, CI
95
37‐66.5, p < 0.0001) and
PFS (54%, CI
95
41.3‐70.6, p < 0.001) but not OS compared to pa-
tients with negative iPET/CT (Figure 1A,B,C). Negative iPET/CT
SUPPLEMENT ABSTRACTS
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245
predicted higher EFS in patients with age >60, male sex, IPI 3‐5 and
stage II‐IV (Figure 1D).
Conclusion: New treatment modalities like CARTs, resulted in
renewed interest in iPET adaptive frontline trial design strategies.
Our results support the prognostic impact of iPET/CT in a prospec-
tive clinical trial setting and helps design and interpretation of
ongoing and future clinical trials evaluating iPET/CT adaptive front-
line trials.
Keywords: PET‐CT, Aggressive B‐cell non‐Hodgkin lymphoma,
Combination Therapies
No conflicts of interest pertinent to the abstract.
172 | BONE MARROW INFILTRATION ASSESSMENT BY FDG
18
‐
PET: CAN THIS IMAGING TEST REPLACE BONE MARROW
TREPHINE BIOPSY IN DIFFUSE LARGE B CELL LYMPHOMA
STAGING?
S. Duarte
1
, C. Afonso
1
, B. Marques
1
, C. Barros Lima
1
, D. Neves
1
, A. C.
Lai
2
, M. J. Julião
2
, A. Roque
1
, L. Ruzickova
1
, J. Carda
1
, M. Gomes
1
, A.
Cipriano
2
, A. Espadana
1
1
Centro Hospitalar e Universitário de Coimbra, Clinical Hematology
Department, Coimbra, Portugal,
2
Centro Hospitalar e Universitário de
Coimbra, Pathology Department, Coimbra, Portugal
Introduction: Bone marrow assessment (BMI) is an important part of
disease staging in lymphoma, and includes FDG
18
‐PET and BM
trephine biopsy (BMB), which is the gold‐standard for detecting BM
infiltration. Nevertheless, studies indicate that PET accurately de-
tects BMI in aggressive lymphomas.
We aimed to assess the accuracy of PET in detecting BMI in
diffuse large B‐cell lymphoma (DLBCL).
Methods: Single centre retrospective analysis of 335 patients (pts)
diagnosed with DLBCL from 2010 to 2019. BMB and PET data at
diagnosis was available in 144 pts. Agreement between PET and BMB
findings was assessed by Cohen's k computation. For survival anal-
ysis, Cox regression model was used.
Results: A total of 144 pts underwent PET and BMB, 57%
males, median age 63 years (22‐89). Positive BMB (BMB+) was
observed in 22 (15%) pts (19 with BMI by DLBCL and 3 by
discordant low‐grade lymphoma). Positive PET (PET+) was
observed in 36 (25%) pts (diffuse BMI pattern in 18 pts, focal in
16 and both in 2 pts). At diagnosis, 92% of all PET+ pts presented
with advanced stage disease due to extra‐medullary organ
involvement (AdS). Concordant detection of BMI by PET and BMB
was observed in 14 pts. Twenty‐two pts with PET+ (out of 36)
were missed by BMB (BMB‐), 12 of these with focal BMI pattern.
BMI was not detected by PET in 8/22 BMB+ pts (2/8 with low‐
grade lymphoma in BMB). Only 8/108 (7%) pts with PET‐ had
BMB+ and 22/122 (18%) pts with BMB‐ showed PET+. We
observed a moderate agreement between PET and BMB (k = 0.36;
p < 0.001).
Considering BMB as the gold standard for BMI, the sensitivity
and specificity of PET for BMI assessment were 64% (95%CI: 41‐
82%) and 82% (95%CI: 74‐88%), respectively. PPV (positive predic-
tive value) was 39% (95%CI: 24‐56%) and NPV (negative predictive
value) was 93% (95%CI: 85‐97%).
In our cohort, the progression free survival (PFS) at 5 years (yrs)
was 58%. Median PFS for BMB‐ and BMB+ was NR (not reached) and
25 months, respectively (HR 1.68; p = 0.097). For BMI by PET, PFS
was NR and 15.8 months for PET‐ and PET+, respectively, signifi-
cantly higher in PET‐ group (HR 2.49; p = 0.001). The negative impact
of PET positivity in PFS became not significant after multivariate
analysis for different prognostic variables.
Total overall survival (OS) at 5 yrs was 67%. Median OS was NR
for both BMB‐ and BMB+ (HR 1.61; p = 0.181; 70% and 53% at 5 yrs)
and NR for both PET‐ and PET+ (HR 1.70; p = 0.084; 72% and 51% at
5 yrs).
Conclusions: We showed a higher specificity of FDG
18
‐PET over
BMB in BMI assessment in DLBCL. In fact, a higher number of pts
presented BMI by PET compared with BMB, which may have failed to
detect focal BMI. However, although we showed that BMI by PET
had a negative impact on global PFS, further studies are necessary to
clarify if BMI adds a negative impact on survival of DLBCL pts with
AdS already in PET staging. Contrastingly, PET sensitivity in detect-
ing BMI was lower which may be related to its low avidity for low
tumour burden and low volume disease.
Keywords: Diagnostic and Prognostic Biomarkers, PET‐CT, Aggres-
sive B‐cell non‐Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
173 | THE ELDERLY PROGNOSTIC INDEX (EPI) PREDICTS
EARLY MORTALITY IN OLDER PATIENTS WITH DLBCL. A
SUBSTUDY OF THE ELDERLY PROJECT BY THE FONDAZIONE
ITALIANA LINFOMI (FIL)
F. Merli
1
, A. Tucci
2
, A. Arcari
3
, L. Rigacci
4
, F. Cavallo
5
, G. Cabras
6
, I.
Alvarez
1
, A. Fabbri
7
, A. Re
2
, S. Ferrero
5
, B. Puccini
4
, S. V. Usai
6
, A.
Ferrari
1
, E. Cencini
7
, E. Pennese
8
, V. R. Zilioli
9
, D. Marino
10
, M.
Balzarotti
11
, M. C. Cox
12
, M. Zanni
13
, A. Di Rocco
14
, A. Lleshi
15
, B.
Botto
16
, S. Hohaus
17
, M. Merli
18
, R. Sartori
19
, G. Gini
20
, L. Nassi
21
, G.
Musuraca
22
, M. Tani
23
, C. Bottelli
2
, S. Kovalchuk
4
, F. Re
24
, L.
Flenghi
25
, A. Molinari
26
, G. Tarantini
27
, E. Chimienti
15
, L.
Marcheselli
28
, C. Mammi
29
, S. Luminari
1
, M. Spina
15
1
Azienda USL‐IRCCS Reggio Emilia, Hematology, REGGIO EMILIA, Italy,
2
ASST Spedali Civili Brescia, Hematology Division, Brescia, Italy,
3
Guglielmo da Saliceto Hospital, Hematology Unit, Piacenza, Italy,
4
Careggi Hospital and University of Florence, Lymphoma Unit, Hematol-
ogy Department, Firenze, Italy,
5
Univesity of Torino, AOU Città della
Salute e della Scienza di Torino, Hematology Division, Torino, Italy,
6
Oncology Hospital Armando Businco, Hematology Division, Cagliari,
Italy,
7
Azienda Ospedaliera Universitaria Senese and Università di Siena,
Hematology Unit, Siena, Italy,
8
Ospedale Spirito Santo, Lymphoma Unit,
246
-
SUPPLEMENT ABSTRACTS
Department of Hematology, Pescara, Italy,
9
ASST Grande Ospedale
Metropolitano Niguarda, Division of Hematology, Milano, Italy,
10
Veneto
Institute of Oncology IOV‐IRCCS, Department of Clinical and Experi-
mental Oncology, Medical Oncology 1, Padova, Italy,
11
Humanitas Clin-
ical Research Hospital‐IRCCS, Department of Medical Oncology and
Hematology, Rozzano, Italy,
12
Azienda Ospedaliera Universitaria S.
Andrea, Hematology Unit, Roma, Italy,
13
Antonio e Biagio e Cesare Arrigo
Hospital, Hematology Unit, Alessandria, Italy,
14
Dept. of Translational and
Precision Medicine “Sapienza”, University of Roma, Institute of Hematol-
ogy, Roma, Italy,
15
Centro di Riferimento Oncologico di Aviano (CRO)
IRCCS, Division of Medical Oncology and Immune‐related Tumors, Aviano,
Italy,
16
Città della Salute e della Scienza Hospital and University, Division
of Hematology, Torino, Italy,
17
University Policlinico Gemelli Foundation‐
IRCCS, Catholic University of the Sacred Heart, Hematology Unit, Roma,
Italy,
18
Ospedale di Circolo e Fondazione Macchi ‐ ASST Sette Laghi,
University of Insubria, Division of Hematology, Varese, Italy,
19
Veneto
Institute of Oncology, IOV‐IRCCS, Department of Clinical and Experi-
mental Oncology, Oncohematology Unit, CastelfrancoVeneto, Italy,
20
Azienda Ospedaliera Universitaria Ospedali Riuniti, Division of Hema-
tology, Ancona, Italy,
21
AOU Maggiore della Carità and University of
Eastern Piedmont, Hematology, Novara, Italy,
22
IRCCS Istituto Romagnolo
per lo Studio dei Tumori (IRST) “Dino Amadori”, Hematology, Meldola,
Italy,
23
Santa Maria delle Croci Hospital, Hematology Unit, Ravenna, Italy,
24
Azienda Ospedaliera Universitaria, Hematology and BMT Center,
Parma, Italy,
25
Santa Maria della Misericordia Hospital, Hematology,
Perugia, Italy,
26
Ospedale degli Infermi, Hematology Unit, Rimini, Italy,
27
Ospedale Monsignor R. Dimiccoli, Haematology and BMT Unit, Barletta,
Italy,
28
Fondazione Italiana Linfomi Onlus, FIL, Modena, Italy,
29
Gruppo
Amici dell'Ematologia, GRADE Onlus, Reggio Emilia, Italy
Introduction: The Elderly Prognostic Index (EPI) is based on the
integration of a simplified geriatric assessment (sGA), haemoglobin
levels, and International Prognostic Index (IPI) and has been vali-
dated to predict overall survival in older patients with Diffuse Large
B‐cell lymphoma (DLBCL) (Merli et al, JCO 2021). In this study we
evaluated the ability of EPI to predict the risk of early mortality in
older DLBCL patients.
Methods: This analysis was conducted starting from the same data-
set of the prospective observational Elderly Project (EP) that has
been used to define the EPI. The main endpoint of this analysis was
early mortality rate defined as death occurring within 90 days from
the date of diagnosis. Starting from EP we only excluded alive pa-
tients with a follow‐up shorter than 90 days. Clinical features,
treatment details, and causes of death were retrieved from the EP
dataset. Treatment was classified in three groups: Full Dose (FD;
> 70% of theoretical dose of anthracycline), Reduced Dose (RD;
< 70%), and Palliative therapy (PT; No anthracyclines). EPI was
calculated as originally reported (Merli et al. JCO 2021) (Figure 1A).
Results: This study was conducted on 1150 out of 1163 patients
retrieved from the EP who were evaluable for the type of therapy
and follow‐up. Median age was 76 years (65 to 94). Thirty‐one
percent were older than 80 years; 55%, 28% and 17% were FIT,
UNFIT , and FRAIL based on sGA. EPI score was 0‐1 (low), 2‐5 (in-
termediate), and 6‐8 (high) in 24%, 48% and 28%, respectively. Time
to Therapy (TTT) was shorter than 15 days in 24%. A pre‐phase
therapy was administered in 14% of patients but details were lack-
ing. Overall, 69 early deaths were observed being 19% of all reported
deaths. The cumulative incidence of early death at 90 days was 6.0%.
Comparing the causes of the deaths occurring earlier or later than 90
days we observed lower frequency of deaths due to lymphoma
progression for early events (42% vs 75%) and higher frequency of
deaths due to toxicity and to infections (32% vs 4% and 22% vs 3%,
respectively). In univariable analysis factors associated with higher
risk of early deaths were age >80 years, sGA, anemia, high risk IPI,
TTT < 15 days, bulky disease, EPI (intermediate and high risk) and the
use of PT. We conducted a multivariable analysis on 931 patients
excluding PT and confirmed an independent prognostic role to pre-
dict Early death for high risk EPI (OR 3.45; 95% CI 1.07–11.2)
(Figure 1B) and for bulky disease (OR 2.09; 95% CI 1.09 – 3.98)
Conclusions: The cumulative incidence of early death for older pa-
tients with DLBCL is not negligible (6%), is mainly associated with
non‐lymphoma related events and suggests the adoption of adequate
preventive measures. For patients treated with an anthracycline
SUPPLEMENT ABSTRACTS
-
247
containing regimen, high risk EPI and bulky disease are independent
factors to predict the risk of dying early during treatment.
The research was funded by: GRADE non profit foundation and
UniCredit Bank
Keywords: Diagnostic and Prognostic Biomarkers, Aggressive B‐cell
non‐Hodgkin lymphoma, Therapeutics and Clinical Trials in Lym-
phoma ‐ Other
No conflicts of interest pertinent to the abstract.
174 | POLATUZUMAB VEDOTIN WITH BENDAMUSTINE AND
RITUXIMAB FOR RELAPSED/REFRACTORY HIGH‐GRADE B‐CELL
LYMPHOMA: THE UK EXPERIENCE
M. Northend
1
, W. Wilson
2
, W. Osborne
3
, C. P. Fox
4
, A. J Davies
5
, D.
El‐Sharkawi
6
, E. H. Phillips
7
, H. W. Sim
8
, S. Sadullah
9
, N. Shah
10
, Y. Y.
Peng
11
, I. Qureshi
12
, J. Addada
13
, R. F. Mora
14
, N. Phillips
15
, A.
Kuhnl
16
, E. Davies
17
, D. Wrench
18
, P. McKay
19
, I. Karpha
20
, A.
Cowley
21
, R. Karim
22
, S. Challenor
23
, V. Singh
24
, C. Burton
25
, R.
Auer
26
, C. Williams
27
, A. Broom
28
, C. Roddie
1
, W. Townsend
1
1
University College London Hospitals NHS Foundation Trust, Department
of Haematology, London, UK,
2
Cancer Research UK & UCL Cancer Trials
Centre, Haematology Trials Team, London, UK,
3
The Newcastle‐upon‐
Tyne Hospitals NHS Foundation Trust, Department of Haematology,
Newcastle‐upon‐Tyne, UK,
4
Nottingham University Hospitals NHS Trust,
Department of Haematology, Nottingham, UK,
5
University of South-
ampton, Southampton Cancer Research UK/NIHR Experimental Cancer
Medicines Centre, Southampton, UK,
6
The Royal Marsden NHS Founda-
tion Trust, Department of Haematology, London, UK,
7
University of
Manchester, The Christie NHS Foundation Trust, Manchester, UK,
8
Lon-
don North West University Healthcare NHS Trust, Department of Hae-
matology, London, UK,
9
James Paget University Hospitals NHS
Foundation Trust, Department of Haematology, Great Yarmouth, UK,
10
Norfolk & Norwich University Hospitals NHS Foundation Trust,
Department of Haematology, Norwich, UK,
11
St George's University
Hospital NHS Foundation Trust, Department of Haematology, London,
UK,
12
University Hospitals Birmingham NHS Foundation Trust, Depart-
ment of Haematology, Birmingham, UK,
13
University Hospitals of Derby &
Burton NHS Foundation Trust, Department of Haematology, Derby, UK,
14
Nottingham University Hospitals NHS Trust, Department of Haema-
tology, Nottingham, UK,
15
University Hospital of North Midlands NHS
Trust, Department of Haematology, Stoke‐on‐Trent, UK,
16
King's College
Hospital NHS Foundation Trust, Department of Haematology, London,
UK,
17
Manchester University NHS Foundation Trust, Department of
Haematology, London, UK,
18
Guy's & St Thomas' Hospitals NHS Foun-
dation Trust, Department of Haematology, London, UK,
19
Beatson West
of Scotland Cancer Centre, Department of Haematology, Glasgow, UK,
20
The Clatterbridge Cancer Centre NHS Foundation Trust, Department of
Haematology, Liverpool, UK,
21
East Sussex Healthcare NHS Trust,
Department of Haematology, East Sussex, UK,
22
Dorset Healthcare Uni-
versity NHS Foundation Trust, Department of Haematology, Dorchester,
UK,
23
Royal Cornwall NHS Trust, Department of Haematology, Truro, UK,
24
Aintree University Hospital, Department of Haematology, Liverpool, UK,
25
Leeds Teaching Hospitals NHS Trust, Department of Haematology,
Leeds, UK,
26
Bart's Health NHS Trust, Department of Haemato‐Oncology,
London, UK,
27
Northumbria Healthcare NHS Foundation Trust, Depart-
ment of Haematology, Hexham, UK,
28
Western General Hospital,
Department of Haematology, Edinburgh, UK
Introduction: For patients with relapsed/refractory (R/R) diffuse
large B‐cell lymphoma (DLBCL) ineligible for stem cell trans-
plantation (SCT) the addition of polatuzumab vedotin to bendamus-
tine and rituximab (Pola‐BR) has been shown to improve
progression‐free survival (PFS) and overall survival (OS). The com-
bination is also increasingly used as bridging to CAR T‐cell therapy
(CAR‐T) and after CAR‐T failure. We aimed to assess its efficacy
when used for these indications via 2 UK early access schemes.
Methods: This retrospective study included patients treated with
Pola‐BR via the Early Access to Medicines Scheme (EAMS) for re‐
induction therapy and Cancer Drugs Fund (CDF) for CAR‐T
bridging at 28 UK hospitals between July 2019‐October 2020. Re-
sponses were investigator‐assessed. Time to event was measured
from the first day of Pola‐BR treatment.
Results: 133 patients were included: 65.4% male; median age 72 (18‐
88); 30.1% performance status (PS) 2‐4; 21.8% bulky disease
(>7.5cm); 64.7% ≥ 2 prior treatments and 68.4% refractory to the
last treatment. The median number of cycles completed was 4 for all
patients and 1 for CAR‐T bridging. Bendamustine was dose reduced
for 36.8% and omitted for 7.5% in at least 1 cycle. The overall
response rate (ORR) was 57.0% (complete response (CR) 32.8%),
median follow‐up was 7.7 months, median PFS 4.8 months and me-
dian OS 8.2 months.
Seventy‐eight patients received Pola‐BR with no planned SCT/
CAR‐T. Of these 78.2% were SCT ineligible due to age, co‐morbidity
or PS. The ORR was 65.8% (CR 40.8%), median PFS 5.4 months and
median OS 10.2 months. Significant factors for shortened PFS by
univariate analysis were bulk disease >7.5cm (HR 2.32 (95% CI 1.23‐
4.38) p = 0.009), ≥2 prior treatments (HR 2.17 (95% CI 1.19‐3.95)
p = 0.01) and refractoriness to last treatment (HR 3.48 (95% CI 1.79‐
6.76) p < 0.001). Significance was maintained in a multivariate model
of these 3 variables.
Forty patients received Pola‐BR as bridging to CAR‐T. The ORR
was 42.1% (CR 18.4%, partial response 23.7%, stable disease 15.8%,
PD 42.1%) and 31/40 (77.5%) proceeded to CAR‐T infusion (N = 5
died due to PD; N = 1 died due infection during bridging; N = 2
infusion pending; N = 1 unavailable).
Sixteen patients received Pola‐BR after CAR‐T failure. The ORR
was 43.8% (CR 18.8%) and 3/16 were successfully bridged to allo-
geneic SCT.
Conclusions: The data from this real‐world cohort of support the use
of Pola‐BR use as an efficacious treatment for SCT ineligible patients
with R/R DLBCL and suggest that bulk disease, number of prior
treatments and response to prior treatment are predictors of PFS.
These data also provide new insights into the use of Pola‐BR as
248
-
SUPPLEMENT ABSTRACTS
bridging prior to CAR‐T and preliminary evidence of efficacy after
CAR‐T failure. The shorter PFS observed in this study compared to
the registration trial may reflect patient selection including a higher
proportion with PS ≥2 and the inclusion of patients with prior CAR‐T.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Chemo-
therapy, Immunotherapy
Conflicts of interests pertinent to the abstract
C. P. Fox
Consultant or advisory role: Roche
Research funding: Roche
Educational grants: Roche
A. J. Davies
Consultant or advisory role: Celgene (A Bristol Myers Squibb Com-
pany), Roche, Kite (A Gilead Company), Takeda, Karyopharm Thera-
peutics, Incyte
Honoraria: Celgene (A Bristol Myers Squibb Company), Roche, Kite
(A Gilead Company), Takeda, Janssen, Acerta Pharm/AstraZeneca,
ADC Therapeutics
Research funding: Celgene (A Bristol Myers Squibb Company), Roche,
Karyopharm Therapeutics, Janssen, Acerta Pharm/AstraZeneca, ADC
Therapeutics, BioInvent
Educational grants: Celgene (A Bristol Myers Squibb Company),
Roche
D. El‐Sharkawi
Consultant or advisory role: Abbvie; ASTEX, AstraZeneca, Beigene,
Janssen, Kyowa Kiirin
Honoraria: Abbvie, AstraZeneca, Janssen, Roche, Takeda
Educational grants: Abbvie, Novartis
N. Shah
Consultant or advisory role: ABBVIE, Janssen, Roche
Educational grants: ABBVIE, Janssen, Roche
A. Kuhnl
Honoraria: Kite, Novartis, Celgene
P. McKay
Consultant or advisory role: Roche
Honoraria: Roche
R. Karim
Honoraria: Bristol Myers Squibb, Roche
V. Singh
Educational grants: Gilead, Novartis, Abbvie
R. Auer
Consultant or advisory role: Beigene
Research funding: Janssen
W. Townsend
Consultant or advisory role: Roche, Gilead, Celgene, Janssen
Honoraria: Roche, Gilead, Celgene, Janssen
175 | BENDAMUSTINE, RITUXIMAB, AND POLATUZUMAB
VEDOTIN FOR RELAPSED OR REFRACTORY DIFFUSE LARGE B‐
CELL LYMPHOMA: SINGLE‐CENTER REAL‐WORLD EXPERIENCE
K. A. Farina
1
, E. Drill
2
, L. W. Buie
1
, L. Falchi
3
, A. Kumar
3
, A. Noy
3
,
M. L. Palomba
3
, G. Salles
3
, D. J. Straus
3
, A. D. Zelenetz
3
, M. J. Buege
1
,
C. L. Batlevi
3
1
Memorial Sloan Kettering Cancer Center, Pharmacy, New York, USA,
2
Memorial Sloan Kettering Cancer Center, Epidemiology & Biostatistics,
New York, USA,
3
Memorial Sloan Kettering Cancer Center, Medicine, New
York, USA
Introduction: In a pivotal phase 2 randomized cohort, addition of
polatuzumab vedotin (pola) to bendamustine and rituximab (BR)
Figure: Overall survival and progression‐free survival (all patients)
SUPPLEMENT ABSTRACTS
-
249
improved rate of complete response (CR), progression‐free survival
(PFS), and overall survival (OS) versus BR alone in patients with
relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL).
Our experience suggests many patients treated with BR‐pola off‐trial
receive fewer cycles and have dose reductions or omissions of
bendamustine potentially impacting response.
Methods: We reviewed adults who received ≥ 1 dose of pola for
R/R DLBCL at Memorial Sloan Kettering Cancer Center between
June 2019 and September 2020. Patients who received pola in a
clinical trial were excluded. We evaluated best response as assessed
by investigator. PFS and OS were estimated by Kaplan Meier
method.
Results: Cohort characteristics and outcomes are described in Table
1 (n = 57). All patients had completed or discontinued pola‐based
treatment at analysis. Median age was 68 years. Patients received
median 3 prior lines of therapy, including prior hematopoietic cell
transplantation (HCT) in 25% and prior chimeric antigen receptor T‐
cell therapy (CAR‐T) in 39%. Patients received median 3 cycles, with
median dose delivered (as percent of US‐approved dosing) of 100%
for both rituximab and pola and 78% for bendamustine. Four patients
(7%) completed 6 cycles. Thirteen patients (23%) proceeded to CAR‐
T. Among 38 patients who received a short course (1 to 3 cycles), 11
patients (29%) proceeded to CAR‐T and 4 patients (11%) proceeded
to HCT.
At median follow‐up of 5 months, CR was achieved in 16%;
partial response (PR) was achieved in 33%. Median time to best
response was 1.6 months. Median PFS and OS were 6 months and 6.3
months, respectively (Figure 1). Univariate analysis did not identify
characteristics associated with response, although an association of
lack of efficacy was noted in patients with double‐hit DLBCL (0% of
responders vs 20% of non‐responders had double‐hit; p = 0.051).
Eleven patients (19%) did not receive bendamustine or only
received bendamustine in cycle 1 (Table 2). Two patients (18%) in this
subgroup responded (both PR; both received ≥ 1 dose of bend-
amustine). Five patients (63%) in this subgroup underwent subse-
quent CAR‐T, 4 of whom did not receive bendamustine.
Conclusions: The observed responses with BR‐pola in our cohort are
lower than trial experience, which may represent enrichment of frail
or heavily pretreated patients who would not have been eligible for
the pivotal phase 2 trial. Relative to the trial, patients received lower
doses and fewer cycles, possibly due to use of BR‐pola as bridging to
CAR‐T/HCT. Notably, 11 of 57 patients – including 4 who received R‐
pola only – proceeded safely to CAR‐T. Study of real‐world outcomes
with BR‐pola in a larger cohort, particularly patients who receive
limited doses of bendamustine and those bridged to CAR‐T/HCT, is
warranted.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Combination
Therapies
Conflicts of interests pertinent to the abstract
250
-
SUPPLEMENT ABSTRACTS
L. Falchi
Consultant or advisory role: Genmab
Research funding: Roche, Genmab
A. Kumar
Consultant or advisory role: Celgene
Research funding: Abbvie, Adaptive Biotechnologies, Celgene, Phar-
macyclics, Seattle Genetics
A. Noy
Consultant or advisory role: Janssen, Pharmacyclics, Medscape,
Targeted Oncology
Research funding: Pharmacyclics, NIH, Raphael Pharma
M L. Palomba
Honoraria: Merck, Celgene, Juno, Pharmacyclics
G. Salles
Consultant or advisory role: Abbvie, Beigene, BMS/Celgene, Debio-
pharm, Genentech/Roche, Genmab, Incyte, Ipsen, Kite/Gilead, Mil-
teniy, Morphosys, Novartis, Velosbio
D. J. Straus
Consultant or advisory role: Seattle Genetics
Research funding: Seattle Genetics
A. D. Zelenetz
Consultant or advisory role: Genentech/Roche, Kite/Gilead, Quant
Health, Astra Zeneca, Karyopharm, Adaptive Biotechnology, Mor-
phoSys, Juno/Celgene/BMS, BeiGene, Verastem
Research funding: MEI Pharma, Genentech/Roche, BeiGene, Adap-
tive Biotechnology
C. L. Batlevi
Honoraria: Dava Oncology
Research funding: Janssen, Novartis, Epizyme, Xynomics
176 | SELINEXOR IN COMBINATION WITH R‐GDP FOR
PATIENTS WITH RELAPSED/REFRACTORY B‐CELL LYMPHOMA:
PRELIMINARY RESULTS OF THE SELINDA PHASE IB LYSA STUDY
(EUDRACT NUMBER: 2015‐005612‐15)
M. Maerevoet
1
, O. Casasnovas
2
, G. Cartron
3
, F. Morschhauser
4
,
C. Thieblemont
5
, K. Bouabdallah
6
, P. Feugier
7
, V. Szablewski
8
,
S. Becker
9
, H. Tilly
10
1
Institut Jules Bordet, ULB, Hematology, Brussels, Belgium,
2
CHU Dijon
Bourgogne, Hematology and INSERM 1231, Dijon, France,
3
CHU
Montpellier, Hematology, Montpellier, France,
4
CHRU Lille, Hematology,
Lille, France,
5
Hôpital St Louis, Hematology, Paris, France,
6
CHU
Bordeaux, Hematology, Bordeaux, France,
7
CHRU Nancy, Hematology,
Nancy, France,
8
CHU Montpellier, Pathological Anatomy and Cytology,
Montpellier, France,
9
Centre Henri Becquerel, Nuclear Medicine, Rouen,
France,
10
Centre Henri Becquerel, Hematology, Rouen, France
Background: Salvage chemotherapy followed by high‐dose therapy
(HDT) and autologous stem‐cell transplantation (ASCT) is the stan-
dard treatment of young patients (pts) with relapsed diffuse large B‐
cell lymphoma (DLBCL). A complete remission before ASCT is the
most important prognosis factor for a better outcome. Selinexor is a
first‐in‐class selective inhibitor of nuclear export, which, through
inhibition of exportin‐1, causes accumulation of tumor suppressor
proteins, reduction in oncoproteins and apoptosis. Selinexor has been
SUPPLEMENT ABSTRACTS
-
251
approved by the US Food and Drug Administration for the treatment
of R/R DLBCL, de novo or transformed from follicular lymphoma (FL)
pts after ≥2 therapies (Kalakonda 2020).
We hereby present preliminary data of a phase IB study
(SELINDA study) evaluating the safety and tolerability of Selinexor
with R‐GDP for pts with B‐cell lymphoma after first or second
treatment failure.
Patients & methods: Eligible pts < 70 years received every 21 days
(d) 3 cycles of rituximab 375 mg/m
2
on d1, dexamethasone 40 mg on
d1 to 4, cisplatin 75 mg/m
2
d1 and gemcitabine 1 gr/m
2
on d1 and 8
(R‐GDP) in combination with escalating doses of Selinexor. The
starting dose (dose level 1, DL1) 40 mg was given on days 1, 3, 8, 10
(Cohort A), and from December 2017 on days 1, 8 and 15 (Cohort B).
The dose‐variation scheme followed a traditional “3+3” design (DL1:
40 mg; DL2: 60 mg), Dose‐limiting toxicities (DLTs) were considered
during the first cycle. DLTs were defined as non‐hematological
toxicity grade (Gr) 3‐4 excluding alopecia, diarrhea and/or nausea/
vomiting and/or fatigue/asthenia, any Gr ≥ 4 hematological toxicity
lasting >7 d, any toxicity resulting in a delay of >14 d of the initiation
of the second cycle.
Results: Between January 2017 and August 2019, 20 pts received
Selinexor‐R‐GDP, 4 pts had FL and, 16 pts had DLBCL. Median age
was 63.5 years (range 45‐70). In 7 pts of cohort A DL1 (selinexor
40 mg on d1, 3, 8, 10), 1 DLT (anorexia grade 3) was observed and
1 pt discontinued treatment during cycle 3 for intolerance (AE Gr
3 . In 6 pts of cohort B DL1 (selinexor 40 mg on d1, 8, 15), no
DLTs were observed; 2 pts discontinued treatment after 2 cy-
cles, 1 for progression and 1 for intolerance (AE + Grade). In 7 pts
of cohort B DL2 (selinexor 60 mg on d1, 8, 15), 1 DLT (neu-
tropenia grade 4 >7d) was observed. Fifteen pts experienced one
or more adverse events, thrombocytopenia gr 4 (5 in the cohort A
40 mg, 2 in the cohort B 40 mg, 3 in the cohort B 60 mg), neu-
tropenia gr 4, (7 in the cohort A 40 mg, 3 in the cohort B 40 mg,
5 in the cohort B 60 mg). Efficacy results will be reported at the
conference.
Conclusion: The recommended dose of weekly selinexor in combi-
nation with R‐GDP was 40 mg on days 1, 8, and 15. The most com-
mon adverse events were Gr 1‐2 non‐hematological or reversible Gr
3‐4 thrombocytopenia or neutropenia. Enrollment for the expansion
is completed.
The research was funded by: Karyopharm
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
M. Maerevoet
Consultant or advisory role: Karyopharm
O. Casasnovas
Consultant or advisory role: Roche, Takeda, MSD, BMS, Gilead
Honoraria: Roche, Takeda, MSD, BMS, Gilead
Research funding: Roche, Gilead
Educational grants: Roche, Amgen
G. Cartron
Consultant or advisory role: Roche, Celgene
Honoraria: Celgene, Roche, Gilead, Sanofi, Abbvie, Novartis, Gilead
H. Tilly
Consultant or advisory role: Karyopharm
177 | LOTIS 2 FOLLOW‐UP ANALYSIS: UPDATED RESULTS
FROM A PHASE 2 STUDY OF LONCASTUXIMAB TESIRINE IN
RELAPSED OR REFRACTORY DIFFUSE LARGE B‐CELL
LYMPHOMA
P. L. Zinzani
1
, P. F. Caimi
2
, C. Carlo‐Stella
3
, W. Ai
4
, J. P. Alderuccio
5
,
K. M. Ardeshna
6
, B. Hess
7
, B. S. Kahl
8
, J. Radford
9
, M. Solh
10
, A.
Stathis
11
, J. Feingold
12
, D. Ungar
12
, Y. Qin
12
, S. He
12
, M. Hamadani
13
1
IRCCS Azienda Ospedaliero‐Universitaria di Bologna Istituto di Emato-
logia “Seràgnoli” and Diagnostica e Sperimentale Università di Bologna,
Dipartimento di Medicina Specialistica, Bologna, Italy,
2
Case Western
Reserve University, University Hospitals Cleveland Medical Center,
Cleveland, USA,
3
Humanitas Clinical and Research Center – IRCCS, and
Humanitas University, Department of Oncology and Hematology, Roz-
zano, Milan, Italy,
4
University of California, Division of Hematology and
Oncology, Department of Medicine, San Francisco, USA,
5
University of
Miami, Sylvester Comprehensive Cancer Center, Miami, USA,
6
University
College London Hospitals NHS Foundation Trust, Department of Hae-
matology, London, UK,
7
Medical University of South Carolina, Division of
Hematology and Medical Oncology, Department of Medicine, Charleston,
USA,
8
Washington University, Department of Medicine, Oncology Divi-
sion, St Louis, USA,
9
Christie NHS Foundation Trust and the University of
Manchester, NIHR Clinical Research Facility, Manchester, UK,
10
Northside
Hospital, Blood and Marrow Transplant Program, Atlanta, Georgia, USA,
11
Oncology Institute of Southern Switzerland, Division of Medical
Oncology, Bellinzona, Switzerland,
12
ADC Therapeutics America, Inc,
Clinical Development, Murray Hill, USA,
13
Medical College of Wisconsin,
Division of Hematology and Oncology, Milwaukee, USA
Introduction: Patients (pts) with relapsed/refractory diffuse large B‐
cell lymphoma (R/R DLBCL) who are ineligible for, or relapse after,
salvage chemotherapy/stem cell transplant (SCT) have a poor prog-
nosis and limited treatment options. Loncastuximab tesirine (Lonca)
comprises a humanized anti‐CD19 antibody conjugated to a potent
pyrrolobenzodiazepine dimer toxin. LOTIS 2 is a Phase 2 study eval-
uating Lonca in patients with R/R DLBCL (NCT03589469). Pts are
being followed‐up, and here, we present updated efficacy and safety
results.
Methods: This multicenter, open label, single‐arm Phase 2 study
enrolled adult pts (≥18 years) with pathologically defined R/R DLBCL
and ≥2 prior systemic treatments. Pts received Lonca 150 µg/kg every
3 weeks (Q3W) for 2 cycles, then 75 µg/kg Q3W thereafter. The pri-
mary efficacy endpoint was overall response rate (ORR), assessed by
central review. Secondary efficacy endpoints included duration of
response (DoR), progression free survival (PFS), and overall survival
252
-
SUPPLEMENT ABSTRACTS
(OS). ORR subgroup analyses were performed. Safety analyses
included treatment‐emergent adverse events (TEAEs). Follow‐up is
every 12 weeks for up to 3 years after the start of treatment.
Results: 145 pts with R/R DLBCL received ≥1 dose of Lonca. Median
age was 66 years (range 23–94) and pts had received a median of 3
prior therapies (range 2–7). At data cut off (October 26, 2020), it was
≥12 months since patients received their first Lonca dose; 2 patients
continue on treatment. Pts had received a mean of 4.6 cycles (std 4.1;
range 1–22) of Lonca.
ORR was 48.3% (complete response [CR]: 24.8%; partial
response [PR]: 23.4%). Median DoR was 12.6 months for responders
(n = 70; patients with CR or PR), and not reached for pts with CR
(Figure 1). Median PFS was 4.9 months and median OS was 9.5
months.
For older pts (≥75 years), ORR was 52.4%. ORR for pts with
double‐/triple‐hit DLBCL was 33.3% and for transformed disease was
44.8%. ORRs for pts refractory to first‐line therapy, most recent
therapy or all prior therapy were 37.9%, 36.9%, and 36.0%,
respectively.
Following Lonca treatment, 15 pts received CD19‐directed
chimeric antigen receptor T‐cell therapy with an investigator‐
assessed ORR of 46.7%, and 11 pts proceeded to SCT as consolida-
tion after responding to Lonca.
The most common (≥25.0%) all‐grade TEAEs were increased
gamma‐glutamyltransferase (GGT) (41.4%), neutropenia (40.0%),
thrombocytopenia (33.1%), fatigue (27.6%), and anemia (26.2%).
Grade ≥3 TEAEs were reported in 107 (73.8%) pts. Treatment‐
related TEAEs leading to treatment discontinuation and dose de-
lays were reported in 26 (17.9%) and 62 (42.8%) pts, respectively;
most common reason for both was increased GGT (16 [11.0%] and 26
[17.9%], respectively).
Conclusions: After longer follow‐up of pts in LOTIS 2, durable re-
sponses to Lonca continue to be observed in heavily pre‐treated pts
with R/R DLBCL. No new safety concerns were reported.
The research was funded by: ADC Therapeutics SA
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Immunotherapy
Conflicts of interests pertinent to the abstract
P. L. Zinzani
Consultant or advisory role: Verastem, MSD, Eusapharma, Sanofi,
ADC Therapeutics, Celltrion, Gilead, Janssen‐Cilag, BMS, Servier,
Sandoz, Roche, Kyowa Kirin, Takeda, TG Therapeutics
P. F. Caimi
Consultant or advisory role: ADC Therapeutics, Kite Therapeutics,
Genentech, Amgen, Verastem, TG Therapeutics, Bayer, Celgene
FIGURE 1 DoR by best overall response
SUPPLEMENT ABSTRACTS
-
253
Research funding: Genentech, ADC Therapeutics
C. Carlo‐Stella
Consultant or advisory role: Boehringer Ingelheim, Sanofi, Servier,
Novartis, Genenta Science srl, ADC Therapeutics, Roche, Karyopharm
Honoraria: Bristol‐Myers Squibb, Merck Sharp & Dohme, Janssen
Oncology, AstraZeneca
Research funding: ADC Therapeutics, Rhizen Pharmaceuticals
W. Ai
Consultant or advisory role: ADC Therapeutics, Nurix, Kymera
Research funding: Nurix Therapeutics
J. P. Alderuccio
Consultant or advisory role: Puma Biotechnology, Inovio Pharma-
ceuticals, Agios Pharmaceuticals, Forma Therapeutics, Foundation
Medicine (immediate family member). ADC Therapeutics (Self)
Other remuneration: OncLive and OncInfo (paid expert testimony)
K. M. Ardeshna
Consultant or advisory role: ADC Therapeutics
Honoraria: Celgene, Gilead, Takeda, Roche, Beigene
Other remuneration: Supported University College London (UCL)/
UCL Hospitals Biomedical Research Unit
B. Hess
Consultant or advisory role: ADC Therapeutics, BMS, AstraZeneca
B. S. Kahl
Consultant or advisory role: ADC Therapeutics, Genentech, Roche
Research funding: ADC Therapeutics
J. Radford
Consultant or advisory role: Takeda, ADC Therapeutics, Bristol
Myers Squibb, Novartis, and Kite Pharma, Seattle Genetics
Stock ownership: AstraZeneca and GlaxoSmithKline (Spouse)
Research funding: Takeda
Other remuneration: Takeda, ADC Therapeutics, Seattle Genetics
(paid expert testimony)
M. Solh
Consultant or advisory role: Amgen, Celgene
Research funding: ADC Therapeutics
A. Stathis
Research funding: Roche, Pfizer, Merck, Bayer, Novartis, MEI‐
Pharma, ADC Therapeutics
Other remuneration: Abbvie, PharmaMar
J. Feingold
Employment or leadership position: ADC Therapeutics
Stock ownership: ADC Therapeutics
D. Ungar
Employment or leadership position: ADC Therapeutics
Stock ownership: ADC Therapeutics
Y. Qin
Employment or leadership position: ADC Therapeutics
Stock ownership: ADC Therapeutics
S. He
Employment or leadership position: ADC Therapeutics
Stock ownership: ADC Therapeutics
M. Hamadani
Consultant or advisory role: Janssen R&D, Incyte Corporation, ADC
Therapeutics, Celgene Corporation, Pharmacyclics, Omeros, AbGe-
nomics, Verastem, TeneoBio, Sanofi Genzyme, AstraZeneca
Research funding: Takeda Pharmaceutical, Spectrum Pharmaceuti-
cals, Astellas Pharma
178 | ESTIMATION OF LONG‐TERM SURVIVAL WITH
TAFASITAMAB + LENALIDOMIDE (LEN) IN RELAPSED/
REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA (R/R DLBCL)
G. Salles
1
, B. Goswami
2
, V. Bagnardi
3
, D. Dey
2
, M. Winderlich
2
,
S. Ambarkhane
4
, D. Huang
2
, G. S. Nowakowski
5
1
Memorial Sloan Kettering Cancer Center, Department of Medicine, New
York, USA,
2
MorphoSys AG, Biostatistics and Data Management, Planegg,
Germany,
3
University of Milan‐Bicocca, Department of Statistics and
Quantitative Methods, Milan, Italy,
4
MorphoSys AG, Clinical Development,
Planegg, Germany,
5
Mayo Clinic, Division of Hematology, Rochester, USA
Introduction: L‐MIND (NCT02399085) is an ongoing, open‐label,
single‐arm, Phase II study of tafasitamab + LEN in patients (pts) with
R/R DLBCL who are ineligible for autologous stem cell transplant.
Progression‐free survival (PFS) strongly correlates with overall sur-
vival (OS); however, while PFS estimates study drug treatment effect,
OS also includes effects of subsequent cancer treatments or pallia-
tive care. Given that not all OS and PFS events may occur even
during a long follow‐up, traditional survival analyses may underesti-
mate survival benefit for tafasitamab + LEN. We estimate the pro-
portion of long‐term survivors (LTS) and survival benefit associated
with tafasitamab + LEN treatment using mixture cure models.
Methods: In the L‐MIND study (data cut‐off: Oct 30, 2020; median
follow‐up 42.7 months), Kaplan–Meier (KM) plots of PFS and OS for
80/81 enrolled pts were observed to plateau after 30 months, with
the majority of events (PFS: 45/46 [97.8%]; OS: 36/41 [87.8%]) re-
ported up to that timepoint. LTS exhibit a high survival benefit from
tafasitamab + LEN treatment, and were defined as pts without a PFS
event and who did not decease after the observed plateau. Thus, the
pt population can be classified into two sub‐populations: LTS and
non‐LTS. A ‘mixture cure model’ was fitted on L‐MIND‐observed PFS
and OS data to estimate the proportion of LTS and associated mean
survival for the two sub‐populations. For comparative purposes,
standard parametric models without considering an LTS proportion
were also fitted on PFS and OS data. Sensitivity analyses were per-
formed considering different survival distributions.
254
-
SUPPLEMENT ABSTRACTS
Results: Using a mixture cure model fitted to PFS and OS data, the
estimated proportion of LTS for the tafasitamab + LEN combination
was 42.5 (95% confidence interval [CI] 30.1‐55.3) and 44.6% (95% CI:
28.1–62.4), respectively. The predicted mean survival when the
mixture cure model was fitted on PFS data was 16.7 years for LTS pts
vs 0.5 years for non‐LTS pts, yielding 7.4 years for the overall pop-
ulation. Further, survival rates for pts with tafasitamab + LEN
treatment were predicted as 40.7% and 36.5% at 2 and 5 years,
respectively. Similar results were obtained when the mixture cure
model was fitted on OS data. By comparison, using a standard
parametric model (Weibull distribution), the predicted mean survival
in the overall population was 3.6 years fitting PFS data (Figure 1A)
and 5.2 years fitting OS data (Figure 1B).
Conclusion: PFS and OS KM curves for the L‐MIND study –
reaching a long plateau and not following a standard Weibull
distribution – suggest the presence of an LTS subgroup. Standard
parametric models may fail to capture the survival plateau of LTS,
leading to a poor estimate of OS benefit in such pts. The mixture
cure model suggests that the treatment of R/R DLBCL pts with
tafasitamab + LEN is associated with a high LTS proportion of
42.5%.
EA – previously submitted to EHA 2021.
The research was funded by: MorphoSys AG, Planegg, Germany
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
G. Salles
Consultant or advisory role: Roche/Genentech, Gilead Sciences,
Janssen, Celgene, Novartis, MorphoSys AG, Epizyme, Alimera Sci-
ences, Genmab, Debiopharm Group, Velosbio
B. Goswami
Employment or leadership position: MorphoSys AG
FIGURE 1 Kaplan‐Meier plot of (A)investigator‐assessed PFS and (B)OS as observed in L‐MIND and predicted outcomes by mixture cure
model and Weibull survival model
SUPPLEMENT ABSTRACTS
-
255
V. Bagnardi
Other remuneration: MorphoSys AG
D. Dey
Employment or leadership position: MorphoSys AG
M. Winderlich
Employment or leadership position: MorphoSys AG
S. Ambarkhane
Employment or leadership position: MorphoSys AG
Educational grants: MorphoSys AG
D. Huang
Employment or leadership position: MorphoSys AG
G. S. Nowakowski
Consultant or advisory role: Celgene, MorphoSys AG, Genentech,
Selvita, Debiopharm Group, Kite/Gilead Sciences
Research funding: Celgene, NanoStringTechnologies, MorphoSys AG
179 | CENTRAL NERVOUS SYSTEM RELAPSE IN PATIENTS
WITH DIFFUSE LARGE B‐CELL LYMPHOMA TREATED WITH R‐
CHOP: STUDY OF THE SPANISH LYMPHOMA GROUP GELTAMO
M. Franch‐Sarto
1
, O. Garcia‐Calduch
1
, A. Rivas
2
, A. Lopez
2
,
E. Gonzalez‐Barca
3
, A. Sureda
3
, M. Baile
4
, A. Martin
4
, A. Salar
5
,
Antonio‐M. Gutierrez
6
, M. Bastos
7
, M.‐J. Rodriguez
8
, S. Gonzalez
9
,
J.‐A. Queizán
10
, R. Cordoba
11
, C. Montalbán
12
, H. D. Luzardo
13
,
P. Abrisqueta
14
, D. Garcia
15
, A. Hong
16
, F.‐J. Peñalver
17
, M. Moreno
1
,
J.‐M. Sancho
1
1
Hospital Universitari Germans Trias i Pujol, Hematology, Badalona,
Spain,
2
Hospital Universitari Clinic, Hematology, Barcelona, Spain,
3
Hospital Duran i Reynalds, Hematology, Bellvitge, Spain,
4
Hospital
Universitario de Salamanca and IBSAL., Hematology, Salamanca, Spain,
5
Hospital del Mar, Hematology, Barcelona, Spain,
6
Hospital Universitari
Son Espases, Hematology, Palma de Mallorca, Spain,
7
Hospital
Universitario Gregorio Marañón, Hematology, Madrid, Spain,
8
Hospital
Universitario de Canarias, Hematology, Canarias, Spain,
9
Hospital
Universitario Marqués de Valdecilla, Hematology, Santander, Spain,
10
Hospital General de Segovia, Hematology, Segovia, Spain,
11
Fundación
Jiméndez Díaz, Hematology, Madrid, Spain,
12
MD Anderson Cancer
Center, Hematology, Madrid, Spain,
13
Hospital Universitario de Gran
Canarias Dr Negrín, Hematology, Las Palmas de Gran Canaria, Spain,
14
Hospital Universitari Vall d'Hebron, Hematology, Barcelona, Spain,
15
Hospital La Zarzuela, Hematology, Madrid, Spain,
16
Hospital de
Lanzarote, Hematology, Lanzarote, Spain,
17
Hospital Fundación Alcorcón,
Hematology, Madrid, Spain
Introduction: Central nervous system (CNS) relapse in diffuse large
B‐cell lymphoma (DLBCL) occurs with an incidence around 5% and is
associated with poor outcomes. The aim of this study was to analyse
the incidence, characteristics, risk factors and outcomes of CNS re-
lapses of DLBCL patients treated with R‐CHOP in the Spanish
GELTAMO group hospitals.
Methods: Retrospective multicentre study of DLBCL patients
without CNS involvement at diagnosis treated with R‐CHOP. Clinical
and biological data and risk factors for CNS relapses were collected,
as well as the type of CNS prophylaxis and outcomes of the CNS
relapses.
Results: A total of 1530 DLBCL patients from 16 hospitals were
included between 1999 and 2016, median age 63 years (range 18‐
91), 50% males. Characteristics at diagnosis are summarized in the
Table. CNS prophylaxis was given to 284 patients (20%): intrathecal
in 244, intravenous high‐dose methotrexate (HDMTX) in 6 and other
in 34.
After a median follow‐up of 4.7 years (range, 0.1‐18), 66 patients
had CNS relapse, with a 2‐years cumulative incidence of CNS relapse
(95% CI) of 3.7% (2.8%, 4.7%), without differences according CNS
prophylaxis vs no‐CNS prophylaxis groups. Characteristics of CNS
relapses were: isolated in CNS in 37 (56%) and systemic plus CNS in
29 (44%); site of CNS relapse was parenchymal in 31 (48%), lep-
tomeningeal in 26 (41%) and both in 7 (11%). The median time to
CNS relapse was 9.1 months (range 1‐116), with 40 (61%) of relapses
in less than 12 months.
In univariate analysis, baseline characteristics associated with
CNS relapse were age ≥60 years, double/triple hit lymphoma, ECOG
> 1, advanced stage, elevated LDH, >1 extranodal involvement, B
symptoms, IPI and involvement of testes, kidney/adrenal glands,
epidural and bone marrow. According to CNS‐IPI, the 2‐year cumu-
lative incidence rates of CNS relapse were 0.9% (0.3%, 2.2%) for the
low risk group (n = 455), 3% (1.9%, 4.6%) for the intermediate risk
group (n = 659), and 10.2% (7.1%, 14%) for the high risk group (n =
306) (p < 0.001). In the multivariate analysis the only risk factor
associated with CNS relapse was the CNS‐IPI (HR [95% CI] 1.7 [1.2‐
2.3], p < 0.001), while bone marrow involvement showed a trend (HR
[95% CI] 1.64 [0.9‐2.9], p = 0.096).
Median overall survival (OS) after CNS relapse (95% CI) was 4.8
months (3, 6.6), significantly higher in those treated with HDMTX‐
based regimens (9.9 months [3.2‐16.5]), than in those treated with
other regimens (5 months [0‐11.5]) or palliative care (0.7 months [0.3‐
1.1]).
Conclusions: The incidence and type of CNS relapse was similar from
those previously described (more often in the first year, isolated in CNS
and with parenchymal involvement). In this series, CNS‐IPI was the
only risk factor associated with CNS relapse. The OS after CNS relapse
was poor, with better outcomes in patients receiving HDMTX.
Table. Clinical characteristics at diagnosis of 1530 DLBCL patients
treated with R‐CHOP.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
256
-
SUPPLEMENT ABSTRACTS
180 | A SINGLE‐CENTER RETROSPECTIVE ANALYSIS OF THE
TOXICITY OF HIGH‐DOSE METHOTREXATE (HDMTX)
ADMINISTERED ON THE FIRST DAY OF (R)CHOP IN AGGRESSIVE
NONHODGKIN LYMPHOMAS (ANHLS)
M. Fleming
1
, Y. Huang
1
, E. Dotson
1
, D. A. Bond
1
, J. Reneau
1
,
N. Epperla
1
, L. Alinari
1
, J. Brammer
1
, B. Christian
1
, R. A. Baiocchi
1
,
K. Maddocks
1
, Y. Sawalha
1
1
The Ohio State University, Internal Medicine, Columbus, Ohio, USA
Introduction: The optimal timing for administering HDMTX when
combined with (R)CHOP is unclear. Wilson et al (Blood Adv 2020)
showed that administration of prophylactic HDMTX before day (D) 10
of RCHOP may be associated with fewer treatment delays, with most
patients (pts) in their dataset receiving HDMTX between D7‐9. Herein,
we report our experience with HDMTX given on D1 of (R)CHOP.
Methods: We identified 140 pts with aNHLs treated from 2012–
2020 with ≥1 cycle of HDMTX combined with (R)CHOP for
prophylaxis against (Cohort 1, n = 84) or treatment of (Cohort 2, n =
56) CNS involvement.
Results: Table 1 shows pt and treatment data. 54% of (R)CHOP cy-
cles in Cohort 1 (242/445) and 90% in Cohort 2 (241/269) included
HDMTX with a median number of HDMTX cycles/pt of 3 and 5,
respectively. HDMTX starting dose was 3.5 g/m2 in all but 4 pts (1.5‐
3 g/m2), given on D1 of (R)CHOP in all MTX‐containing cycles but 4
(3 D2, 1 D8). (R)CHOP was prematurely discontinued in 7 pts (8%) in
Cohort 1 and 16 (29%) in Cohort 2, most commonly due to toxicity in
TABLE 1 Psst and treatment characteristics
Variable, n (%)
Cohort 1: CNS
prophylaxis N =
84
Cohort 2: CNS
involvement N =
56
Age, median (range) 58 (19‐76) 62 (19‐80)
Male 57 (68) 32 (57)
Lymphoma subtype
DLBCL 79 (94) 41 (73)
High‐grade 5 (6) 9 (16)
T‐cell 0 0 3 (5)
Primary CNS 0 0 1 (2)
Other 0 0 2 (4)
ECOG PS ≥2 7 (8) 18 (36)
CNS‐IPI, high‐risk 40 (48) ‐
No. of HDMTX cycles/pt,
median
3 5
1‐2 15 (18) 11 (20)
3‐4 64 (76) 13 (23)
5‐6 5 (6) 33 (59)
G‐CSF
All cycles 371 (86) 256 (95)
HDMTX cycles 239 (99) 240 (100)
Reason for (R)CHOP
discontinuation
N = 7 pts N = 16 pts
Toxicity 4 (47) 1 (6)
Progression 0 0 3 (19)
Death 1 (14) 8 (50)
Alternative therapy 1 (14) 3 (19)
Other 1 (14) 1 (6)
Reason for ≥7D treatment
delay
N = 11 cycles N = 12 cycles
Myelosuppression 5 (45) 1 (8)
Infection/neutropenic fever 4 (36) 6 (50)
Mucositis 1 (9) 1 (8)
AKI 1 (9) 1 (8)
Other 0 0 3 (25)
SUPPLEMENT ABSTRACTS
-
257
Cohort 1 (57%) and progression/death (69%) in Cohort 2. Treatment
was delayed ≥7D in 11 cycles (3%) in Cohort 1 and 12 (6%) in Cohort
2. Doxorubicin and/or cyclophosphamide were dose‐reduced in 9
cycles (2%) in Cohort 1 and 12 (4%) in Cohort 2. HDMTX was pre-
maturely discontinued without/before (R)CHOP discontinuation in
11 (13%) pts in Cohort 1 and 5 (9%) in Cohort 2. In Cohorts 1 and 2,
respectively, acute kidney injury (AKI) grade (G) ≥2 occurred in 6%
and 14% of cycles, neutropenic fever (NF) in 6% and 9%, G3/4
elevated AST/ALT in 2% and 2%, and G3/4 mucositis in 2% and 4%.
Glucarpidase was administered in 8 cycles. 70% of NF events in
Cohort 1 and all in Cohort 2 occurred during HDMTX‐containing
cycles. In Cohort 1, NF was more common when HDMTX was first
administered in cycle 1 of (R)CHOP (n = 46) compared with cycles 2‐
4 (n = 38): 24% (11/46) vs 3% (1/38), p = .01.The rates of CNS
relapse in Cohorts 1 and 2 were 7% and 25% with median follow‐up
of 23 and 28 months, respectively.
Conclusions: To our knowledge, this is the largest study reporting on
the safety and deliverability of HDMTX given on D1 of (R)CHOP. (R)
CHOP treatment delays, dose reductions and discontinuations due to
toxicities were uncommon. Delaying prophylactic HDMTX beyond
cycle 1 of (R)CHOP might lower the risk of NF.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma Chemotherapy
Conflicts of interests pertinent to the abstract
B. Christian
Consultant or advisory role: Genentech, Verastem, AstraZeneca and
Seattle Genetics
Research funding: Genentech, BMS/Celgene, Triphase, Acerta, Mil-
lenium, Merck, Morphosys, and Seattle Genetics
Y. Sawalha
Consultant or advisory role: TG Therapeutics
Research funding: TG Therapeutics, BMS, BeiGene
181 | SAFETY AND EFFICACY OF THE “CARMEN” REGIMEN, A
NEW DOSE‐DENSE SHORT‐TERM THERAPY IN PATIENTS WITH
AGGRESSIVE B‐CELL LYMPHOMA AND MYC REARRANGEMENT
A. J. M. Ferreri
1
, P. Angelillo
1
, F. Erbella
1
, C. Liberatore
1
,
C. Cattaneo
2
, L. Verga
3
, A. Lleshi
4
, B. Allione
5
, F. Facchetti
6
,
M. Ponzoni
7
, C. Pagani
2
, M. Foppoli
1
, L. Pecciarini
6
, M. C. Sassone
1
,
E. Flospergher
1
, G. Rossi
2
, M. Spina
8
, A. Re
2
1
IRCCS San Raffaele Scientific Institute, Department of Onco‐Hematology,
Milan, Italy,
2
Spedali Civili di Brescia, UOC Ematologia, Brescia, Italy,
3
Azienda Ospedaliera San Gerardo, Divisione di Ematologia, Monza, Italy,
4
Centro Riferimento Oncologico , Oncologia Medica, Aviano, Italy,
5
AOU
Città della Salute e della Scienza di Torino, SC Ematologia, Torino, Italy,
6
Spedali Civili di Brescia, Servizio di Anatomia Patologica, Brescia, Italy,
7
IRCCS San Raffaele Scientific Institute , Anatomia Patologica, Milan,
Italy,
8
IRCCS Centro Riferimento Oncologico, SOC Oncologia Medica e
Tumori Immunocorrelati, Aviano, Italy
Introduction: Patients (pts) with aggressive B‐cell lymphoma and
MYC rearrangement exhibits poor outcome after R‐CHOP treatment.
In the last decade, these pts were treated with a new dose‐dense,
short‐term therapy termed “CARMEN”, at several Italian Centers.
Excellent efficacy and safety profile have been reported in HIV/AIDS
pts with high‐risk Burkitt lymphoma (BL) [Ferreri et al. BJH 2021],
but its efficacy in pts with high‐grade B‐cell lymphoma with MYC
rearrangement (HGBCL) remains to be defined. Herein, we report a
retrospective series of consecutive pts with BL or HGBCL treated
with CARMEN regimen.
Methods: Either HIV‐negative and HIV‐positive pts aged 18‐80
years with BL or HGBCL and MYC rearrangement positive by
FISH were treated with CARMEN regimen, which includes a single
36‐day induction course of sequential doses of cyclophosphamide,
vincristine, rituximab, methotrexate, VP16, and doxorubicin
plus intrathecal chemotherapy, followed by consolidation with
HD‐cytarabine ± cisplatin. Pts who did not achieve complete
remission (CR) after induction received BEAM/ASCT after
consolidation.
Results: 63 pts (22 HGBCL; 41 BL) received the CARMEN regimen
(Table). Treatment was well tolerated: 56 (89%) pts completed the
induction, and 55 (87%) completed the consolidation. G4 hemato-
logical toxicity during induction was neutropenia in 48 (76%) pts,
thrombocytopenia in 24 (38%) and anemia in 7 (11%), which were
recorded after consolidation in 34 (62%), 38 (69%) and 1 (2%) pt,
respectively. G4 non hematological toxicity was uncommon: muco-
sitis in 4 (6%) pts and tumor lysis syndrome in 1 (2%) during induc-
tion, and heart failure and bleeding in 1 (2%) pt each after
consolidation. G4 infections were recorded in 4 (6%) pts during in-
duction and in 2 (3%) after consolidation. Induction and consolidation
doses were reduced in 6 (9%) and 4 (7%) pts, respectively. Seven
HGBCL and 9 BL pts received ASCT, with expected tolerability. 4
HGBCL and 2 BL pts died of toxicity (sepsis in 4; respiratory failure;
COVID‐19), with a TRM of 9%.
After induction, 18 (82%) HGBCL and 37 (90%) BL pts achieved a
response, which was CR in 10 (45%) and 26 (63%) pts, respectively.
After the whole treatment, 15 (68%) HGBCL pts and 32 (78%) BL pts
achieved a CR, and, at a median follow‐up of 54 (2‐131) months, 15
(100%) HGBCL and 29 (91%) BL pts remain relapse‐free, with a 5‐yr
PFS of 67% and 70%, respectively. 15 HGBCL and 32 BL pts are alive,
with a 5‐yr OS of 66% and 77%, respectively. HIV seropositivity did
not modify outcome. Age and LDH level were independently asso-
ciated with OS.
Conclusions: With the limitations of a retrospective series, this study
shows that CARMEN is a safe and active treatment both in HIV‐
negative and –positive pts with HGBCL and MYC rearrangement
and BL. Survival figures in HGBCL pts compare favorably with results
reported with R‐CHOP or analogous, and are similar to those ach-
ieved in BL pts.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma Pathology and
Classification of Lymphomas Chemotherapy
No conflicts of interest pertinent to the abstract.
258
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SUPPLEMENT ABSTRACTS
182 | UPDATED RESULTS OF A PHASE 2 STUDY FROM
GELTAMO INVESTIGATING THE COMBINATION OF IBRUTINIB
WITH R‐GEMOX IN PATIENTS WITH RELAPSED OR REFRACTORY
DIFFUSE LARGE B‐CELL LYMPHOMA
B. Rey Búa
1
, A. Jiménez‐Ubieto
2
, J. J. Sánchez Blanco
3
,
P. Abrisqueta
4
, A. Gutiérrez
5
, Án. Ramírez‐Páyer
6
, E. Giné
7
, I. Zeberio
Etxetxipia
8
, M. José Terol
9
, F. de la Cruz
10
, R. Andreu
11
, M.
Ramírez
12
, A. de la Fuente
13
, M. Viguria
14
, M. Peñarrubia
15
,
C. Grande
2
, S. Montes‐Moreno
16
, M. D. Caballero Barrigón
1
,
A. Martín García‐Sancho
1
1
Hospital Universitario de Salamanca and IBSAL, Hematology
Department, Salamanca, Spain,
2
Hospital 12 de Octubre, Hematology
Department, Madrid, Spain,
3
H. Morales Meseguer, Hematology
Department, Murcia, Spain,
4
Hospital Vall d’Hebron, Hematology
Department, Barcelona, Spain,
5
H. Son Espases, Hematology Department,
Palma de Mallorca, Spain,
6
Hospital Central de Asturias, Hematology
Department, Oviedo, Spain,
7
H. Clinic de Barcelona, Hematology
Department, Barcelona, Spain,
8
Hospital Universitario de Donostia,
Hematology Department, Donostia‐San Sebastian, Spain,
9
H.C. Valencia,
Hematology Department, Valencia, Spain,
10
Hospital Virgen del Rocio,
Hematology Department, Sevilla, Spain,
11
Hospital la Fe, Hematology
Department, Valencica, Spain,
12
H. Especialidades Jerez de la Frontera,
Hematology Department, Jerez, Spain,
13
MD Anderson CC, Hematology
Department, Madrid, Spain,
14
Complejo Hospitalario de Navarra, Hema-
tology Department, Pamplona, Spain,
15
Hospital Clínico Universitario de
Valladolid, Hematology Department, Valladolid, Spain,
16
H. Universitario
Marqués de Valdecilla, Pathology Department, Santander, Spain
Introduction: In the present phase II clinical trial (NCT02692248), we
investigated the efficacy and toxicity of the combination of Ibrutinib
with R‐GEMOX‐D (rituximab, gemcitabine, oxaliplatin and dexa-
methasone), in patients with non‐germinal center B‐cell like (non‐
GCB) diffuse large B‐cell lymphoma (DLBCL).
Methods: We included patients with histological diagnosis of non‐
GCB DLBCL (Hans algorithm), with relapsed or refractory disease
and non‐candidates for autologous stem‐cell transplantation. Pa-
tients received an induction treatment with 6 (in case of complete
remission [CR] after cycle 4) or 8 (in case of partial response [PR] or
stable disease after cycle 4) cycles of R‐GEMOX‐D at standard doses
every 2 weeks, in combination with ibrutinib (560 mg daily), followed
by a maintenance treatment with ibrutinib for a maximum of 2 years.
The primary objective was to evaluate the overall response rate
(ORR) after 4 cycles. Analyses were performed in the intention to
treat population (data cut‐off 16
th
January 2021).
Results: Sixty‐four patients (59.4% male) were included. Median age
was 67 (25‐84) years. Patients had received a median of 2 previous
lines of treatment; 61% were refractory (<PR) to the last regimen.
FIGURE 1 Overall survival (OS) and progression free survival (PFS) in the overall series (A, B) and according to status of lymphoma at
study entry (C,D)
SUPPLEMENT ABSTRACTS
-
259
ORR and CR rate after 4
th
cycle were 53.1% and 34.4%, respectively.
Patients with non‐refractory disease had significantly higher ORR
(76% vs 38%, p = 0.003) and CR rate (72% vs 10%, p < 0.01) than
patients with refractory disease. At the end of induction, ORR and CR
rate were 35.9% and 29.7%, respectively. Twenty‐four (37%) patients
started maintenance with ibrutinib, but only 7 completed it. After a
median follow‐up of 29 months (0.37‐48.9), the estimated 2‐year PFS
and OS were 20% and 27%, respectively (Figure 1A and 1B), being
significantly better in patients with non‐refractory disease (Figure 1C
and 1D). In the multivariate analysis, status of lymphoma (refractory
vs non‐refractory) significantly influenced PFS (HR 3.03; 95% CI 1.6‐
5.7; p < 0.01) and OS (HR 2.2; 95% CI 1.2‐4.2; p = 0.016) indepen-
dently from the IPI and the number of previous treatment lines. The
most frequent grade 3‐5 adverse events (AE) (>10% of patients)
were thrombocytopenia (51.6%), neutropenia (46.9%), anemia
(21.9%), lymphocyte count decreased (17.2%) and diarrhea (15.6%).
Three patients presented a grade 5 AE, two of them related (asper-
gillosis and pneumonia, respectively) and one unrelated (heart
failure).
Conclusions: The combination of ibrutinib with R‐GEMOX‐D as
salvage therapy for patients with non‐GCB DLBCL is associated with
high response rates, especially in non‐refractory patients. The vast
majority of refractory patients progress very early, so this regimen
could be considered as a bridge to other consolidation therapies.
Biological studies analyzing cell of origin by gene expression profiling,
minimal residual disease and mutational spectrum are in progress.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Molecular
Targeted Therapies, Combination Therapies
No conflicts of interest pertinent to the abstract.
183 | DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) IN LATE‐
OCTOGENARIAN (LO) PATIENTS: A SUBSTUDY OF THE “ELDERLY
PROJECT” BY THE FONDAZIONE ITALIANA LINFOMI (FIL)
A. Tucci
1
, F. Merli
2
, A. Fabbri
3
, S. Mancuso
4
, R. Sartori
5
, S. Storti
6
,
S. Luminari
7
, C. Mammi
8
, L. Marcheselli
9
, A. Arcari
10
, F. Cavallo
11
,
V. R. Zilioli
12
, C. Bottelli
1
, A. Re
1
, G. Gini
13
, M. C. Cox
14
, B. Puccini
15
,
C. Pagani
1
, M. Balzarotti
16
, M. Spina
17
, G. Rossi
1
1
ASST Spedali Civili Brescia, Hematology Division, Brescia, Italy,
2
Azienda
Unità Sanitaria Locale – IRCCS, Hematology Unit, Reggio Emilia, Italy,
3
zienda Ospedaliera Universitaria Senese and University of Siena, Unit of
Hematology, Siena, Italy,
4
Department Pro.Mi.Se, Univeristy of Palermo ,
Haematology Division, Palermo, Italy,
5
Veneto Institute of Oncology, IOV‐
IRCCS, Department of Clinical and Experimental Oncology, Oncohema-
tology Unit, Castelfranco Veneto (TV), Italy,
6
Università Cattolica , Onco‐
hematology Unit, Campobasso‐Roma, Italy,
7
University of Modena and
Reggio Emilia, Azienda Unità Sanitaria Locale – IRCCS, Department
CHIMOMO, Hematology Unit, Reggio Emilia, Italy,
8
Gruppo Amici del-
l'Ematologia GRADE‐ Onlus Foundation, Hematology Unit, Reggio Emilia,
Italy,
9
Fondazione Italiana Linfomi Onlus, Fondazione Italiana Linfomi
Onlus, Modena, Italy,
10
Ospedale Guglielmo da Saliceto, Hematology Unit,
Piacenza, Italy,
11
University of Torino/AOU “Città della Salute e della
Scienza di Torino”, Division of Hematology, Department of Molecular
Biotechnologies and Health Sciences, Torino, Italy,
12
ASST Grande Ospe-
dale Metropolitano Niguarda, Division of Hematology, Milano, Italy,
13
Azienda Ospedaliera Universitaria Ospedali Riuniti, Division of Hema-
tology, Ancona, Italy,
14
Azienda Ospedaliera Universitaria S.Andrea, He-
matology Unit, Roma, Italy,
15
Careggi University Hospital, Hematology
Unit, Firenze, Italy,
16
Humanitas Clinical Research Hospital‐IRCCS,
Department of Medical Oncology and Hematology, Rozzano (MI), Italy,
17
Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Division of
Medical Oncology and Immune‐related Tumors, Aviano (PN), Italy
Introduction: Octogenarians are increasingly attending haemato-
logical departments and treatment of aggressive lymphoma is chal-
lenging in this category of patients (pts). Comprehensive geriatric
assessment (CGA) has proven useful in guiding treatment decisions
and it is now widely recommended. Several studies have reported the
results of treatment in octogenarians of median age 83 years.
However, age limits for delivering potentially curative treatment are
increasing. Aim of this study was to focus on late octogenarians (LO),
aged >84, investigating their characteristics and trying to define the
best treatment strategy.
Methods: We studied all consecutive pts aged ≥80, registered in
the FIL Elderly Project, a large prospective study on elderly DLBCL
where a simplified GA (sGA) was applied and the elderly prognostic
index (EPI) was built (Merli, JCO 2021). Pts were classified ac-
cording to age, sGA and EPI. Treatment was based on clinician
decision and intensity was defined according to the relative dose of
anthracycline delivered: full dose (FD) 70‐100%, reduced dose
(RD) <70% and palliative (PT) 0%. Primary endpoint was overall
survival (OS).
Results: Of 1163 fully evaluable pts, 370 (32%) were ≥80 and 129 of
them were over 84 (LO). After a median of 30 months (1‐59), 3‐y OS
was altogether 51%. It differed significantly in UNFIT vs FRAIL pts
(60 vs 43% p 0.001) and in pts with Intermediate vs High EPI score
(71 vs 41% p < 0.001). According to treatment, no difference in 3‐y
OS was observed in pts receiving FD (62%) or RD (61%), while PT
resulted in worse survival (27%). The 3‐y OS in LO was significantly
worse than in early octogenarians (EO) aged 80‐84 (37 vs 57% p
0.001). These two age groups had similar clinical and geriatric char-
acteristics, but differed in treatment intensity received, with 50% of
LO receiving palliation vs 23% of EO, regardless of their fitness (ta-
ble 1). However, 3‐y OS of UNFIT pts treated with RD was similar in
LO (69%) as in EO (70%), whereas LO receiving PT did not reach long
term survival. Notably, the outcome of pts receiving PT was markedly
better when RTX was included in PT (38 vs 9% p 0.007).
Conclusions: This study emphasizes the risk of undertreating pts
relying only on very advanced age. A curative intent approach with
reduced anthracycline dose was the best choice even in late
260
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SUPPLEMENT ABSTRACTS
octogenarians identified by sGA as not FRAIL. In FRAIL pts the in-
clusion of RTX in palliative treatment should be considered.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
L. Marcheselli
Consultant or advisory role: Sandoz spa, free of charge
184 | LONG‐TERM OUTCOMES OF ELDERLY PATIENTS
TREATED WITH FRONTLINE R‐CHOP: UPDATE OF THE LNH03‐
6B TRIAL
V. Camus
1
, Aurél. Belot
2
, L. Oberic
3
, D. Sibon
4
, H. Ghesquières
5
,
C. Thieblemont
6
, C. Fruchart
7
, O. Casasnovas
8
, Jean‐M. Michot
9
,
T. J. Molina
10
, A. Bosly
11
, Clém. Joubert
2
, C. Haioun
12
, R. Delarue
4
,
H. Tilly
1
1
Centre Henri Becquerel, Department of Hematology, Rouen, France,
2
LYSARC, Statistics, Pierre‐Bénite, France,
3
IUCT Oncopole, Hematology,
Toulouse, France,
4
CHU Necker, hematology, Paris, France,
5
CHU Lyon
Sud, Hematology, Pierre‐Bénite, France,
6
CHU St Louis, Hematology,
PARIS, France,
7
CH DUNKERQUE, HEMATOLOGY, DUNKERQUE,
France,
8
Dijon University Hospital, Hematology, Dijon, France,
9
Institut
Gustave Roussy, Hematology, Villejuif, France,
10
CHU Necker, Pathology,
Paris, France,
11
UCL Mont‐Godinne, Hematology, Namur, Belgium,
12
CHU
Mondor, Hematology, Créteil, France
Introduction: Approximately half of patients (pts) with diffuse large B
cell lymphoma (DLBCL) are older than 60 years (yrs). Long term
outcomes (≥10 yrs) data after frontline R‐CHOP are scarce. LNH03‐
6B trial was a multicentric, phase III, randomized trial evaluating the
efficacy of R‐CHOP delivered every 2 weeks (R‐CHOP14) or 3 weeks
(R‐CHOP21) with or without darbepoetin alfa (DA) in pts aged 60‐80
yrs with previously untreated DLBCL with age‐adjusted IPI (aaIPI) ≥1
(Lancet Oncol 2013;14:525‐33). We implemented a prospective
long‐term follow‐up (LTFU) program at end of this trial to evaluate
long term (LT) outcomes of these pts.
Methods: All pts included in the LNH03‐6B trial were analyzed, and
LTFU was obtained from centers participating to the LTFU program.
Primary endpoint was progression‐free survival (PFS). Secondary
endpoints were: overall survival (OS), first relapse patterns and
treatments, autologous stem cell transplant (ASCT) rate, PFS and OS
TABLE 1 TABLE
SUPPLEMENT ABSTRACTS
-
261
after the second line of therapy (PFS2/OS2), and secondary malig-
nancies (SM) rate. Non‐parametric Kaplan‐Meier estimator was used
for the PFS, OS, PFS2 and OS2.
Results: Between December 2003 and December 2012, 600 pts were
randomized in LNH03‐6B trial in four countries. 304 and 296 pts
intended to receive 8 cycles of R‐CHOP14 or R‐CHOP21, respectively.
LT outcomes data were investigated for 164/259 (63%) pts eligible to
the LTFU program (lost to follow‐up: n = 92, pts’ opposition: n = 3).
With a median follow‐up of 10.1 yrs, 213 pts progressed including 87
pts with a primary refractory disease and 140 pts died without pro-
gression. Ten‐year PFS was: 41% (95% CI: 35‐47) in the R‐CHOP14
group and 40% (33‐46) in the R‐CHOP21 group (p = 0.92,
Figure 1A). Ten‐year OS was based on 302 deaths, and estimated as
50% (43‐56) in both randomization groups (p = 0.98). Causes of death
were similar in thetwogroups,mainlyrepresentedbylymphoma(43%).
SM occurred in 73 (12%) pts including 18 squamous cell carcinoma.
Salvage regimens were at the discretion of the investigators.
Data from 194 of the 213 pts were analyzed. Two main sets were
identified in this analysis: intensive chemotherapy (R‐DHAOX/R‐ICE/
R‐ESHAP, n = 99) and standard chemotherapy (R‐GEMOX, R‐
BENDAMUSTINE, n = 72. Rituximab was used in 2
nd
line in 134
pts (71%) and radiotherapy in 28 pts (14%). Twenty pts (10%)
received ASCT (median age at randomization: 64 yrs). 105 pts /213
(49%) progressed after 2
nd
line therapy and 77 pts died without a
second progression (36%). The 2‐yr PFS2 and OS2 probabilities were
21% (16‐27, Figure 1B) and 39% (32‐45), respectively. 2‐yr PFS2 in
the set of ASCT recipients was 60% (36‐78).
Conclusions: PFS and OS were similar between groups 10 yrs after
randomization. Progression leaded to very unfavorable prognosis
except for a small set of selected pts that received ASCT. New al-
ternatives, including CAR‐T cells therapy, need to be explored as a
second line treatment in this population.
Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Chemotherapy
No conflicts of interest pertinent to the abstract.
185 | PROGRESSION‐FREE SURVIVAL AT 24 MONTHS AS A
LANDMARK AFTER AUTOLOGOUS STEM CELL TRANSPLANT IN
RELAPSED OR REFRACTORY DIFFUSE LARGE B‐CELL
LYMPHOMA
A. M. Tun
1
, S. Maliske
2
, Y. Wang
3
, M. J. Maurer
4
, I. N. Micallef
3
,
D. J. Inwards
3
, L. F. Porrata
3
, A. C. Rosenthal
5
, M. Kharfan‐Dabaja
6
,
J. Orme
3
, B. K. Link
7
, J. R. Cerhan
4
, C. A. Thompson
3
, T. M. Haber-
mann
3
, T. E. Witzig
3
, S. M. Ansell
3
, G. S. Nowakowski
3
, U. Farooq
2
,
P. B. Johnston
3
1
The university of Kansas, Division of hematologic malignancies and
cellular therapeutics, Westwood, Kansas, USA,
2
University of Iowa,
Division of Hematology, Oncology, and Blood & Marrow Transplantation,
Iowa City, USA,
3
Mayo Clinic, Division of Hematology, Rochester,
Minnesota, USA,
4
Mayo Clinic, Department of Health Sciences Research,
Rochester, USA,
5
Mayo Clinic, Division of Hematology, Mayo Clinic,
Phoenix, USA,
6
Mayo Clinic, Division of Hematology/Oncology,
Jacksonville, USA,
7
University of Iowa, Department of Internal Medicine,
Iowa, USA
Background: Patients with newly diagnosed diffuse large B‐cell
lymphoma (DLBCL) who achieve event‐free survival at 24
months (EFS24) following immunochemotherapy (IC) have excel-
lent overall survival (OS) similar to that of age‐ and sex‐matched
general population. The standard of care for patients with
relapsed or refractory (RR) DLBCL following frontline IC is salvage
therapy followed by autologous stem cell transplant (ASCT). The
goal of this study is to evaluate the role of progression‐free sur-
vival (PFS) at 24 months (PFS24) as a landmark after ASCT in
patients with RR DLBCL.
Methods: Patients with RR DLBCL after frontline R‐CHOP or R‐
CHOP‐like IC who underwent salvage therapy and ASCT at Mayo
Clinic or University of Iowa between 07/2000 and 4/2020 were
identified from institutional lymphoma transplant databases. Clinical
characteristics, treatment information, and outcome data were
FIGURE 1 (A) Long‐term Progression free survival (PFS) according to first‐line treatment arm (R‐CHOP14 versus R‐CHOP21) (B):
progression‐free survival after first progressing (PFS2)
262
-
SUPPLEMENT ABSTRACTS
abstracted. Post‐ASCT PFS, OS, and post‐relapse survival (PRS) were
plotted by Kaplan‐Meier method, and cumulative incidences of
relapse vs non‐relapse mortality (NRM) and different causes of death
were compared accounting for competing events. Statistical analyses
were performed in EZR v1.54.
Results: A total of 437 patients were identified. Median age at
ASCT was 61 years (range 19‐78), and 280 (64%) were male. After
a median post‐ASCT follow up of 8.0 years (95% CI 7.2‐8.7), 215
patients had a relapse (or disease progression), 180 within 2 years
and 35 after 2 years. For the entire cohort, post‐ASCT relapse
rate was much higher than NRM rate (48.1 vs 9.1% at 5‐year).
Median PFS and OS after ASCT was 2.7 and 5.4 years, respec-
tively. Lymphoma was the primary cause of death after ASCT. In
contrast, for patients who had achieved PFS24 (n = 220), rates of
post‐PFS24 relapse and NRM were similar (14.8% and 12.3% at 5‐
year). Median PFS and OS after achieving PFS24 was 10.0 and
11.5 years, respectively. Lymphoma related and unrelated death
rates were similar after achieving PFS24 (Table). For all patients
who had a post‐ASCT relapse, median PRS was 0.7 years (95% CI
0.5‐0.9), and late relapse (>2 vs ≤2 years after ASCT) was asso-
ciated with better PRS (median 2.3 [1.7‐4.8] vs 0.5 [0.3‐0.7] years,
p < 0.001).
Conclusions: Post‐ASCT PFS24 is an important prognostic predictor
of post‐ASCT outcomes in patients with RR DLBCL following front-
line IC.
Starting landmark
Achieved
ASCT (n = 437) PFS24 (n = 220)
5‐year rate of (%)
Relapse 48.1 (43.2‐52.8) 14.8 (10.1‐20.3)
NRM 9.1 (6.5‐12.2) 12.3 (7.8‐17.8)
Median PFS, years 2.7 (1.5‐4.3) 10.0 (8.4‐13.1)
5‐year PFS (%) 42.8 (38.0‐47.6) 72.9 (65.6‐78.9)
Median OS, years 5.4 (4.2‐7.4) 11.5 (9.9‐NA)
5‐year OS (%) 51.9 (46.9‐56.7) 79.3 (72.3‐84.8)
5‐year rate of deaths
from (%)
LymphomaTreatment‐
related
complicationsOther
causesUnknown
causes
36.0 (31.3‐0.40.6)
6.3 (4.2‐8.9)4.8
(3.0‐7.3)1.0 (0.3‐
2.5)
6.5 (3.4‐11.0)4.2
(1.8‐8.1)8.1
(4.6‐12.9)1.8
(0.5‐4.9)
Keywords: Late Effects in Lymphoma Survivors, Aggressive B‐cell
non‐Hodgkin lymphoma, Stem Cell Transplant
Conflicts of interests pertinent to the abstract
M. Kharfan‐Dabaja
Consultant or advisory role: Daiichi Sankyo
186 | IMPACT OF TIME TO RELAPSE AND RESPONSE TO
SALVAGE THERAPY ON POST AUTOLOGOUS STEM CELL
TRANSPLANT OUTCOMES IN RELAPSED OR REFRACTORY
DIFFUSE LARGE B‐CELL LYMPHOMA
A. M. Tun
1
, Y. Wang
2
, S. Maliske
3
, U. Farooq
3
, I. N. Micallef
2
,
D. J. Inwards
2
, L. F. Porrata
2
, S. M. Ansell
2
, A. C. Rosenthal
4
, M. Kharfan‐
Dabaja
5
, B. K. Link
3
, J. C. Villasboas
2
, J. Paludo
2
, J. R. Cerhan
6
,
T. M. Habermann
2
, T. E. Witzig
2
, G. S. Nowakowski
2
, P. B. Johnston
2
1
The university of Kansas, Division of hematologic malignancies and
cellular therapeutics, Westwood, Kansas, USA,
2
Mayo Clinic, Division of
Hematology, Rochester, Minnesota, USA,
3
University of Iowa, Division of
Hematology, Oncology, and Blood & Marrow Transplantation, Iowa City,
USA,
4
Mayo Clinic, Division of Hematology, Mayo Clinic, Phoenix, USA,
5
Mayo Clinic, Division of Hematology/Oncology, Jacksonville, USA,
6
Mayo
Clinic, Department of Health Sciences Research, Rochester, USA
Background: The current standard of care for patients with relapsed
or refractory (RR) diffuse large B‐cell lymphoma (DLBCL) following
frontline immunochemotherapy (IC) is salvage therapy, followed by
high‐dose chemotherapy and autologous stem cell transplant (ASCT)
rescue in patients responding to salvage therapy. Time to first relapse
(or refractory status) and response to salvage therapy in patients
with RR DLBCL may reflect the chemosensitivity of the underlying
disease. The aim of this study is to determine whether these factors
impact post‐ASCT outcomes.
Methods: Patients with DLBCL that relapsed after R‐CHOP or R‐
CHOP‐like frontline therapy who underwent salvage therapy and
ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/
2020 were identified from institutional lymphoma and transplant
databases. Clinical characteristics, treatment information, and
outcome data were abstracted. Progression‐free survival (PFS) and
overall survival (OS) from the time of ASCT were analyzed using
Kaplan‐Meier method and Cox proportional hazards models.
Results: A total of 437 patients with RR DLBCL who underwent
salvage therapy and ASCT were identified. 280 (64%) were male.
Median time from initial diagnosis to 1
st
relapse/salvage was 1.0
years (range 0.1‐16.4). A median of 1 line (range 1‐3) of salvage
therapy was required. Response prior to ASCT was complete
response (CR) in 211 (48%), partial response in 199 (46%), stable
disease in 24 (5%), and unknown in 3 (1%) patients. Median age at
ASCT was 61 years (range 19‐78), and median follow up after ASCT
was 8.0 years (95% CI 7.2‐8.7). Median PFS and OS was 2.7 (95% CI
1.5‐4.3) and 5.4 (4.2‐7.4) years, respectively. Time to 1
st
relapse/
salvage (≤1 vs 1‐2 vs >2 years) was not associated with PFS (median
0.8 vs 2.4 vs 4.9 years, p = 0.170) but was associated with OS (2.4 vs
7.4 vs 6.8 years, p = 0.013). Patients who required >1 line of salvage
therapy had significantly inferior PFS (median 0.3 vs 4.5 years, p <
0.001) and OS (0.9 vs 7.4 years, p < 0.001). In addition, patients who
failed to achieve a CR prior to ASCT had significantly worse PFS
(median 0.8 vs 5.3 years, p < 0.001) and OS (2.7 vs 9.2 years, p <
0.001). In multivariate Cox regression models adjusted for age and
sex, time to 1
st
relapse/salvage was not associated with PFS (p =
SUPPLEMENT ABSTRACTS
-
263
